Development Of Retinopathy Research Articles

Analysis of the Association between In Vitro Fertilization/Assisted Conception and the Development of Retinopathy of Prematurity in Very-Low-Birth Weight Newborns.

The objective is to study to what extent the development of retinopathy of prematurity (ROP) is associated with assisted conception (AC) and in vitro fertilization (IVF) in a tertiary referral hospital. This study is a retrospective observational cohort study. Very-low-birth weight (VLBW) infants with gestational age (GA) <32 weeks or birth weight <1500 g were admitted to the neonatal unit of a tertiary care hospital between January 1, 2011, and December 31, 2021. The study determined the degree of ROP developed according to the type of fertilization used for conception. Main outcome measures were ROP prevalence in pregnancies obtained after IVF/intracytoplasmic sperm injection (ICSI) in the period from January 1, 2011, to December 31, 2021, in a tertiary hospital. Of the 408 infants included in the study sample, 105 (25.7%) were born following AC and 12.4% of these developed ROP. In our sample, the practice of IVF was not associated with an increase in the incidence of VLBW infants (R2 = 0.12; P = .29). Conception achieved via AC or IVF is not significantly associated with ROP in any degree of severity.

Serum Iron Status and Retinal Degenerative Diseases: A Mendelian Randomization Study on AMD, RP, and DR.

Background: Observational studies have noted that patients with certain retinal degenerative diseases exhibit iron disturbances in the retina or vitreous compared to healthy controls. However, the connection between serum iron status and these diseases remains unclear. This study aims to explore the potential causal relationship between serum iron status biomarkers and the development of age-related macular degeneration (AMD), retinitis pigmentosa (RP), and diabetic retinopathy (DR). Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal relationship between serum iron status and several retinal degenerative diseases. Genome-wide association study (GWAS) summary-level data were extracted from public GWAS databases. Inverse-variance weighting (IVW), MR-Egger regressions, Simple model, Weighted median, and Weight mode were used as MR methods. Sensitivity analysis was conducted to confirm the robustness of the results by examining horizontal pleiotropy and heterogeneity through MR-Egger intercept and leave-one-out analysis. Results: The MR analysis revealed causal relationships between genetically predicted serum iron status biomarkers and various retinal diseases. Transferrin was positively associated with the odds of AMD (whether dry or wet) (OR = 1.167, 95% CI = 1.045-1.304, p = 0.006) and wet AMD (OR = 1.194, 95% CI = 1.018-1.402, p = 0.030). Ferritin was negatively associated with the odds of wet AMD (OR = 0.555, 95% CI = 0.333-0.927, p = 0.024). Serum iron (OR = 0.508, 95% CI = 0.260-0.993, p = 0.048) and transferrin saturation (OR = 0.508, 95% CI = 0.260-0.993, p = 0.048) were negatively associated with the odds of RP. Conclusions: These findings provide evidence supporting a potential causal relationship between serum iron status and various retinal degenerative diseases, highlighting a direction for future research into the underlying mechanisms of these diseases.

The role of cholesterol crystals and ocular crystal emboli in retinal pathology

Cholesterol crystals (CC) can be responsible for a range of clinical syndromes in the retina from asymptomatic plaques to retinal artery occlusion with clinical trials providing evidence for the efficacy in lipid lowering therapies in preventing ocular pathology. Much of the literature has focused on CC in retinal circulation as a marker of poor systemic health and have attempted to use them to categorize risk of mortality and stroke. More recently cholesterol accumulation and CC formation have been linked to development of diabetic retinopathy with CC formation in the retina due to aberrant retinal cholesterol homeostasis and not simply systemic dyslipidemia.

Investigating the relationship between blood metabolites and diabetic retinopathy using two-sample mendelian randomization and in vivo validation

We addressed fundamental questions about the influence of metabolites on the development of Diabetic retinopathy (DR), and explored the related pathological mechanism. Genome-wide association study (GWAS) database data for metabolites and DR were used to perform Mendelian randomization (MR) studies. The inverse variance weighting (IVW) was chosen as the primary analysis method. Sensitivity analysis was conducted using MR-PRESSO, leave-one-out and Cochran’s Q test. Confounding factors were eliminated to ensure robustness. We also conducted metabolic pathway analysis. In vivo experimental validation was conducted using Sprague Dawley rats. The serum metabolites of the DR group rats and normal group rats were examined to evaluate the MR results. The screen identified eighteen metabolites associated with DR risk, twelve of which were known components. Seven metabolites were positively correlated with DR risk, while five could reduce it. Eight metabolites associated with proliferative DR (PDR) risk were identified, four of which are known components. Three of these were positively associated with PDR risk and one metabolite reduced PDR risk. Additionally, two possible metabolic pathways involved in the biological mechanism of DR were identified. The ELISA results showed that the serum levels of isoleucine and 4-HPA were significantly increased in DR rats, while the level of inosine was decreased. This study offers novel insights into the biological mechanisms underlying DR. Metabolites that are causally linked to DR may serve as promising biomarkers and therapeutic targets.

The role of oxidative stress in retinal diseases

Oxidative stress plays a key role in the pathogenesis of many diseases associated with aging, including atherosclerosis, neurodegenerative diseases, diabetes, and retinal diseases. The retina is a tissue that is particularly susceptible to the adverse effects of oxidative stress, as it is characterized by high metabolic rate and high oxygen consumption compared to other body tissues. This review article discusses the relationship between the cellular mechanisms of impaired prooxidant-antioxidant homeostasis and the development of age-related macular degeneration and diabetic retinopathy. Natural defense mechanisms of maintaining redox homeostasis and therapeutic strategies based on the use of antioxidants are also described.

Development and Novel Therapeutics in Diabetic Retinopathy.

Diabetic retinopathy (DR) is a complication of diabetes mellitus which causes retinal damage which when left untreated will cause visual problems. As the prevalence of DR increases over the years, there is a need to optimise the currently available treatments as well as developing novel drugs to improve the therapy provided for the patients in the clinical practice. Several pharmacological therapies like, anti-vascular endothelial growth factor and anti-inflammatory therapies which include intravitreal, and implant of corticosteroids are significant in the management to decrease the risk of DR-related vision impairment. Clinical trials for novel drug therapies are still ongoing till this day to enhance the efficacy of DR treatment. Even though there are also modern treatments such as laser therapy for the patients, prevention should be done to lower the number of individuals affected by DR. Due to the complexity of DR, there are numerous obstacles to develop new medications for DR which include the increasing healthcare cost of DR treatment. New insights such as utilisation of artificial intelligence will be implemented into the management of DR as it has proved its potential in aiding the screening process. In parallel with the increase in DR prevalence and the number of treatments developed, extensive understanding of the mechanism of action of DR should be further improved to prevent more complications in the future. This review summarises the epidemiological trend, prevention strategies, challenges in treatment, current novel therapeutics (including drugs under clinical trials), future therapeutic trends and possibilities for implementing AI in the early diagnosis and management of DR.

The Role of Arginase and some Parameters in Diabetic Type 2 Patients with and without Retinopathy

Background: Oxidative stress plays a major role in the pathogenesis of diabetes mellitus by damaging cellular organelles and enzymes in blood such as arginase1, insulin and glutathione s-transferase; increasing lipid peroxidation such as malondialdehyde and increasing insulin resistance which can lead to diabetic complications such as diabetic retinopathy. Objectives: To explore the relationship of oxidative stress to the development of diabetic retinopathy by measuring the levels of Arginase1, the activity of glutathione s-transferase enzyme, and the levels of malondialdehyde as a secondary product of lipid peroxidation (biomarker for oxidative stress). Patients and MethodsThis study was conducted from November 2022 to January 2023 at the Ibn Al-Haitham Teaching Eye Hospital in Baghdad, the University of Baghdad / Department of Chemistry and the National Diabetes Centre for Treatment and Research at Al-Mustansyrriah University. This study was conducted on 120 subjects distributed as follows: 40 non-diabetic obese controls, 40 type 2 diabetics with no retinopathy, and 40 type 2 diabetic retinopathy patients, between 30 and 65 years of age. All groups were subjected to tests: measuring fasting blood glucose (FBG), HbA1c, lipid profile (cholesterol, triglycerides, HDL- cholesterol, LDL- cholesterol, and VLDL cholesterol), serum total arginase1, malondialdehyde glutathione s -transferase, body mass index (BMI), and waist-to-hip ratio. Results: Mean arginase1 levels were significantly higher in diabetic patients than in diabetic retinopathy and control groups (p ≤ 0.05). The mean xidative stress marker malondialdehyde concentration was significantly higher in diabetic retinopathy patients than in type 2 diabetics and the control group (P ≤ 0.05). The mean glutathione s-transferase activity in diabetic retinopathy patients was significantly higher than in the control group and type 2 diabetics (P ≤ 0.05). Conclusion: There is a relationship between oxidative stress and the development of diabetic retinopathy, where the levels of arginase1 and malondialdehyde increased and the activity of glutathione s –transferase enzyme increased as a result of oxidative stress and inflammation associated with complications of type 2 diabetes.

Role of ferroptosis in mitochondrial damage in diabetic retinopathy

Diabetic retinopathy is driven by oxidative stress-mitochondrial damage. Activation of ROS producing cytosolic NADPH oxidase 2 (Nox2) in diabetes precedes retinal mitochondrial damage, initiating a vicious cycle of free radicals. Elevated ROS levels peroxidize membrane lipids increasing damaging lipid peroxides (LPOs). While glutathione peroxidase 4 (GPx4) neutralizes LPOs, an imbalance in its generation-neutralization leads to ferroptosis, which is characterized by increased LPOs, free iron and decreased GPx4 activity. Mitochondria are rich in polyunsaturated fatty acids and iron and have mitochondrial isoform of GPx4. Our aim was to investigate mitochondrial ferroptosis in diabetic retinopathy, focusing on Nox2 mediated ROS production. Using human retinal endothelial cells, incubated in 5mM or 20mM D-glucose for 12 to 96 hours, with or without Nox2 inhibitors (100μM apocynin, 5μM EHop-016 or 5μM Gp91 ds-tat), or ferroptosis inhibitors (1μM ferrostatin-1, 50μM deferoxamine) or activator (0.1μM RSL3), cytosolic and mitochondrial ROS, LPOs, iron, GPx4 activity, mitochondrial integrity (membrane permeability, oxygen consumption rate, mtDNA copy numbers) and cell death were quantified. High glucose significantly increased ROS, LPOs and iron levels and inhibited GPx4 activity in cytosol, and while Nox2 and ferroptosis inhibitors prevented glucose-induced increase in ferroptosis markers, mitochondrial damage and cell death, RSL3, further worsened them. Furthermore, high glucose also increased ferroptosis markers in the mitochondria, which followed their increase in the cytosol, suggesting a role of cytosolic ROS in mitochondrial ferroptosis. Thus, targeting Nox2-ferroptosis should help break down the self-perpetuating vicious cycle of free radicals, initiated by the damaged mitochondria, and could provide novel therapeutics to prevent/retard the development of diabetic retinopathy.

Management of diabetic retinopathy in pregnancy

Introduction The onset and development of diabetic retinopathy are more common during pregnancy. Pregnancy has no long-term effect on diabetic retinopathy; however, in 50-70% of cases, changes in retinopathy continues. The probability of worsening is highest in the second trimester and up to one year postpartum. Additional factors that have been associated with disease progression include duration of diabetes, the degree of retinopathy at the time of conception, management of hyperglycemia, anemia, and development of associated hypertension. In cases of severe non-proliferative retinopathy, it is recommended to promptly initiate laser photocoagulation rather than wait for early proliferative changes. Maintaining good diabetic control before and during pregnancy can help prevent disease progression and serious vision loss. Material and methods Diabetic retinopathy management in pregnancy was the subject of a comprehensive review of the scientific and medical literature. A structured search was performed in the PubMed, Scopus and HINARI databases, considering relevant articles published in the last 10 years. The search terms used (in English) were: „Diabetic retinopathy”; „pregnancy”; „laser photocoagulation”; „intravitreal steroids”; „anti-vascular endothelial growth factor”. Results It is suggested that women with diabetes receive pre-conception and post-pregnancy counselling from a multidisciplinary team including an ophthalmologist, endocrinologist, and perinatologist, as diabetic retinopathy may worsen during pregnancy. The risk of progression of the disease and the importance of appropriate metabolic control before and during pregnancy should be clearly explained to the patient. Careful monitoring is required in patients with advanced gestation, significant retinopathy, concomitant hypertension, and nephropathy. Conclusion The risk of retinopathy development may increase during pregnancy. Serious effects can arise for both the mother and the fetus, even though retinopathy is not common during pregnancy. It is possible to avoid significant retinopathy by carefully planning a young diabetic woman's pregnancy and proceeding promptly to laser photocoagulate in cases of severe non-proliferative retinopathy. A tendency for regress is frequently seen in diabetic retinopathy during the post-natal period. Subsequent pregnancies do not significantly increase the risk of progression if the retinopathy is stable before pregnancy.

Impact of glucagon-like peptide-1 receptor agonists on diabetic retinopathy: A meta-analysis of clinical studies emphasising retinal changes as a primary outcome.

To determine if glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with the development and progression of diabetic retinopathy (DR). A systematic search was conducted on PubMed, Cochrane Library, and Embase from inception to February 2024 to identify clinical studies reporting the development of and changes in DR as the primary outcome in patients with type 2 diabetes taking GLP-1RA, insulin, or oral antidiabetic medication (OAD). Two researchers independently completed the search and referred to a third as necessary. Data for meta-analysis was pooled using a random-effects model. Analysis of seven studies representing 242 537 patients showed a significantly decreased risk of incidence of DR between GLP-1RA and insulin use (RR = 0.66, 95% CI (0.48, 0.91), p = 0.01). There was no difference in the risk of DR complications (e.g., vitreous haemorrhage, retinal detachment, or requiring treatment with intravitreal injections, lasers, vitrectomy). Between GLP-1RA and OAD use, there was no difference in the risk of incidence of DR, while there was a significantly increased risk of DR complications (RR = 1.39, 95% CI (1.07, 1.80), p = 0.01). Our findings indicate no elevated risk of incidence of DR linked to GLP-1RA compared to insulin. In fact, GLP-1RA may offer potential advantages over insulin regarding the overall incidence of DR. The increased risk of DR requiring treatment and associated complications in the GLP-1RA group compared to OAD may be due to the transient progression of DR associated with a rapid decrease in HbA1c - a phenomenon not specific to GLP-1RA and warrants further investigation.

The application and clinical translation of the self-evolving machine learning methods in predicting diabetic retinopathy and visualizing clinical transformation.

This study aims to analyze the application and clinical translation value of the self-evolving machine learning methods in predicting diabetic retinopathy and visualizing clinical outcomes. A retrospective study was conducted on 300 diabetic patients admitted to our hospital between January 2022 and October 2023. The patients were divided into a diabetic retinopathy group (n=150) and a non-diabetic retinopathy group (n=150). The improved Beetle Antennae Search (IBAS) was used for hyperparameter optimization in machine learning, and a self-evolving machine learning model based on XGBoost was developed. Value analysis was performed on the predictive features for diabetic retinopathy selected through multifactor logistic regression analysis, followed by the construction of a visualization system to calculate the risk of diabetic retinopathy occurrence. Multifactor logistic regression analysis revealed that being male, having a longer disease duration, higher systolic blood pressure, fasting blood glucose, glycosylated hemoglobin, low-density lipoprotein cholesterol, and urine albumin-to-creatinine ratio were risk factors for the development of diabetic retinopathy, while non-pharmacological treatment was a protective factor. The self-evolving machine learning model demonstrated significant performance advantages in early diagnosis and prediction of diabetic retinopathy occurrence. The application of the self-evolving machine learning models can assist in identifying features associated with diabetic retinopathy in clinical settings, enabling early prediction of disease occurrence and aiding in the formulation of treatment plans to improve patient prognosis.

An assessment of the vision-related quality of life among adult patients with diabetes mellitus in Accra, Ghana

PurposeTo assess the overall vision-related quality of life (VRQoL) of adults with diabetes mellitus attending selected diabetic and eye care facilities in Accra, Ghana. MethodsThis was a hospital-based analytical cross-sectional study which took place from January to July 2023. A purposive consecutive sampling technique was used to select 150 participants. A questionnaire consisting of the WHO-PBD/VF20 and EuroQol Five Dimensional Scale instruments was used to obtain information pertaining to the demographic characteristics, vision-related quality of life and health-related quality of life of selected participants. ResultsThe median participant age was 61.0 years. Participants with diabetic retinopathy had a worse mean overall total VRQoL score (19.4) than those without (79.9) in all domains; general visual functioning, 41.3 vs. 78.7, p = 0.002; general functioning, 15.1 vs. 80.2, p = 0.001; psychosocial, 35.7 vs. 79.3, p = 0.001; and visual symptoms, 24.4 vs. 80.4, p = 0.001. Participants with diabetic retinopathy also had a worse mean overall HRQoL score (17.4) than those without (81.0) in all domains; mobility, 32.4 vs. 79.6, p = 0.001; self-care, 53.9 vs. 77.6, p = 0.001; usual activities, 30.2 vs. 79.8, p = 0.001; pain/discomfort, 36.3 vs. 79.2, p = 0.001; and anxiety, 31.5 vs. 79.7, p = 0.001. ConclusionOur findings suggest a significant deterioration in both vision-related and health-related quality of life with the development of diabetic retinopathy. They highlight the need for nationwide screening programs to identify people with diabetes mellitus, as well as effective glycemic control to prevent the development of complications such as diabetic retinopathy.

Glucagon-Like Peptide-1 Receptor Agonists are Not Associated with an Increased Risk of Progressing to Vision-Threatening Diabetic Retinopathy

ABSTRACT Purpose Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used to treat type 2 diabetes mellitus (DM) by augmenting insulin release and sensitivity. We assessed the overall risk for development of vision-threatening diabetic retinopathy (VTDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME), among GLP-1RA users. Methods A retrospective cohort of patients with NPDR newly started on a GLP-1RA from a national insurance claims database was compared to a cohort of patients treated with other oral anti-diabetic agents and matched for age, sex, race, index year, and number of active diabetic medications. Exclusions occurred for < 2 years in the database before diagnosis; prior diagnoses of PDR, DME, vitreous hemorrhage, and/or other retinal vascular diseases; and prior intraocular treatment for VTDR. Results A total of 6093 users of GLP-1RA were matched to 14,122 controls. In the GLP-1RA cohort, 632 (10.1%), 76 (1.2%), and 544 (8.9%) patients progressed to VTDR, PDR, or DME, respectively. This is compared to 1332 (9.5%) VTDR, 165 (1.2%) PDR, or 1148 (8.1%) DME in the control group. Accounting for underlying DM severity with IPTW, no difference in hazard was seen in the GLP-1RA cohort compared to controls for progression to VTDR (HR = 1.02, 95%CI: 0.92–1.14 p = 0.69), DME (HR = 1.06, 95%CI: 0.95–1.1.9, p = 0.31), or PDR (HR = 0.81, 95%CI: 0.58–1.12, p = 0.20). Conclusion We found no difference in the risk for vision-threatening diabetic retinopathy, nor for its component diseases, DME or PDR, with GLP-1RA use compared to other oral anti-hyperglycemic agents in patients with NPDR.

P191 CO-EXISTING HYPERTENSION: AN INDEPENDENT RISK FACTOR FOR DIABETIC RETINOPATHY IN TYPE-2 DIABETES

Background and Objectives: Hypertension has plausible reason to be show the interaction due to its independent effect on retina. Epidemiological studies also provide clue that for hypertension as a possible effect modifier in the risk development of retinopathy in diabetic patients. It is worth exploring whether subgroup in diabetic population with Hypertension have different risk potential of developing retinopathy. The present study aimed to assess the association of hypertension as a risk factor for diabetic retinopathy (DR) in type 2 diabetes mellitus. Methods: A total of 977 type-2 diabetic patients recruited retrospectively in 2008 from Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM) based on hospital records for determining the incidence of diabetic retinopathy (DR), who were naı̈ve type-2 diabetes during 1993. At the end of 15 year follow-up 495 patients were diagnosed as DR by retinal colour photography. Data on diabetes and lipid profile with serum creatinine, blood pressure and biophysical measures were obtained at baseline, 5, 10 and 15 years follow-up. Binary logistic regression model was used to assess the associations of co-existing hypertension with retinopathy risk adjusting for clinical, biochemical and anthropometric variables. Results: In all three follow-up points, including at baseline, mean systolic and diastolic blood pressure were found to significantly higher among patients who developed DR (P&lt;.001). Binary logistic regression model confirmed coexisting hypertension (OR 3.2; 95% CI 2.2 -4.7) as a significant risk factor of DR adjusting for possible confounders; serum creatinine (OR 21.9; 95% CI 14.0 -35.4) and glycemic control status (OR 17.2; 95% CI 9.4 -31.4). Interaction between hypertension, glycemic control and raised serum creatinine did not appear to be statistically significant (P&gt;0.05). Conclusions: Co-existing hypertension is a significant risk factor of DR irrespective of nephropathy or glycolic control status among Type 2 diabetes mellitus.

A retrospective study of the incidence, patterns, and risk factors of retinopathy of prematurity in infants with birth weight &gt;1500 g in a South Indian tertiary care hospital

Abstract: OBJECTIVE: The objective of the study was to determine the incidence, patterns, and risk factors for the development of retinopathy of prematurity (ROP) in infants weighing &gt;1500 g at birth. MATERIALS AND METHODS: A retrospective analysis was done of the ROP screening records between April 2019 and March 2022. All the infants with birth weight &gt;1500 g who underwent ROP screening were included. Data collected included demographic details, details of the risk factors (respiratory distress syndrome [RDS], hypoxia, anemia, septicemia, patent ductus arteriosus, congenital heart disease [CHD], i.e., atrial septal defects or ventricular septal defects, and multiple gestations), and ocular examination findings. Statistical analyses included calculation of mean, range, Chi-square test, and bivariate logistic regression for associations of risk factors with ROP. RESULTS: ROP was noted in 16.6% of the 336 eyes of 168 infants. The mean birth weight and mean gestational age (GA) of the infants were 1850 ± 33 g and 33.33 weeks ± 1.71 weeks, respectively. Eighteen eyes (32.1%) had Stage I, 17 eyes (30.35%) had Stage II, and 11 eyes (19.64%) had Stage III ROP in Zone II. Aggressive ROP was seen in 8 eyes (14.28%) and stage 5 ROP in two eyes (0.59%). Male gender, GA, CHD, and RDS showed a statistically significant association with the development of ROP in these infants. CONCLUSION: ROP was seen in 16.66% of our subjects. Treatment was required in 6.25% of infants. Risk factors for the development of ROP were low gestational age, male gender, the presence of RDS, and congenital heart disease.

Hyperbilirubinemia and retinopathy of prematurity: a retrospective cohort study.

Retinopathy of prematurity (ROP) is a vasoproliferative retinal disease in preterm infants. Oxidative stress plays a key role in the pathogenesis of ROP. Due to its antioxidant effects, bilirubin has been proposed to be protective against ROP. This study explored the association between hyperbilirubinemia and ROP. We analyzed a 10-year cohort from a neonatal intensive care unit in Milan, Italy, including 1606 infants born under 32 weeks and/or < 1500 g. Data from 1606 infants meeting specific inclusion criteria were reviewed. Eighty infants were excluded due to lack of data, 1526 were deemed eligible for analysis, and 1269 had hyperbilirubinemia requiring phototherapy. There was a higher incidence of ROP among infants with hyperbilirubinemia (13.8%) versus those without (7.8%, p<0.01). Infants with any ROP, non-severe or severe ROP, were exposed to hyperbilirubinemia for a significantly higher number of days compared with those without ROP. Each additional day of exposure increases the risk of developing any ROP by 5%, non-severe ROP by 4%, and severe ROP by 6%. However, this correlation was not observed in infants with gestational age less than 27 weeks and/or body weight less than 1000 g. Conclusion: Our data show that hyperbilirubinemia requiring phototherapy is associated with an increased risk of developing ROP. However, severe hyperbilirubinemia and ROP share many of their risk factors. Therefore, rather than being a risk factor itself, hyperbilirubinemia may be a surrogate for other risk factors for ROP. Clinical Trial Registration: NCT05806684. What is Known: • The development of retinopathy of prematurity (ROP) is influenced by several critical risk factors, including low gestational age, low birth weight, supplemental oxygen use, and increased oxidative stress. • In vitro, unconjugated bilirubin is an effective scavenger of harmful oxygen species and a reducing agent, highlighting its potential protective role against oxidative stress. What is New: • Hyperbilirubinemia requiring phototherapy was associated with an increased risk of developing ROP, but this association was not observed in the most vulnerable population of extremely preterm infants. • Every additional day of phototherapy for hyperbilirubinemia increases the risk of ROP by 5% for any ROP, 4% for non-severe ROP, and 6% for severe ROP.

Risk factors for the time to development of retinopathy of prematurity in premature infants in Iran: a machine learning approach

BackgroundRetinopathy of prematurity (ROP), is a preventable leading cause of blindness in infants and is a condition in which the immature retina experiences abnormal blood vessel growth. The development of ROP is multifactorial; nevertheless, the risk factors are controversial. This study aimed to identify risk factors of time to development of ROP in Iran.MethodsThis historical cohort study utilized data from the hospital records of all newborns referred to the ROP department of Farabi Hospital (from 2017 to 2021) and the NICU records of infants referred from Mahdieh Hospital to Farabi Hospital. Preterm infants with birth weight (BW) ≤ 2000 g or gestational age (GA) < 34 wk, as well as selected infants with an unstable clinical course, as determined by their pediatricians or neonatologists, with BW > 2000 g or GA ≥ 34 wk. The outcome variable was the time to development of ROP (in weeks). Random survival forest was used to analyze the data.ResultsA total of 338 cases, including 676 eyes, were evaluated. The mean GA and BW of the study group were 31.59 ± 2.39 weeks and 1656.72 ± 453.80 g, respectively. According to the criteria of minimal depth and variable importance, the most significant predictors of the time to development of ROP were duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of Total Parenteral Nutrition (TPN), mother age, birth order, number of surfactant administration, and on time screening. The concordance index for predicting survival of the fitted model was 0.878.ConclusionOur findings indicated that the duration of ventilation, GA, duration of oxygen supplementation, bilirubin levels, duration of antibiotic administration, duration of TPN, mother age, birth order, number of surfactant administrations, and on time screening are potential risk factors of prognosis of ROP. The associations between identified risk factors were mostly nonlinear. Therefore, it is recommended to consider the nature of these relationships in managing treatment and designing early interventions.

Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non-consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA-metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC-MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti-inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm-born infants.

Predictive value of serum inflammatory markers in retinopathy of prematurity

PurposeTo evaluate the relationship between the development of retinopathy of prematurity (ROP) and neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR).Material and methodsThe medical records of 153 preterm infants born before the 34th week of gestation, were retrospectively reviewed. Complete blood cell (CBC) and C-reactive protein (CRP) results measured within the first 24 h of life were recorded. NLR, LMR and PLR were calculated by dividing neutrophil count by lymphocyte count, lymphocyte count by monocyte count, and platelet count by lymphocyte count, respectively. Analysis of possible risk factors related with ROP development was evaluated using logistic regression analysis. Results were compared between infants with and without ROP.ResultsA total of 153 infants, of which 64 (41.9%) with ROP and 89 (58.1%) without ROP, were included in the study. While lymphocyte count and LMR were found to be significantly lower in infants with ROP (p = 0.015 and p = 0.044), neutrophil count and NLR were found to be significantly higher (p = 0.021 and p = 0.046, respectively). No significant difference were observed in platelet and monocyte count and PLR (p = 0.808, p = 0.170 and p = 0.075, respectively). Multivariate logistic regression analysis revealed that gestational age, birth weight and NLR were major risk factors for the development of ROP (OR:0.59; p = 0.01, OR:1.00; p = 0.02 and OR: 2.56; p = 0.02, respectively).ConclusionThis study supports that, in addition to prematurity, NLR on the first postnatal day has a significant predictive value in ROP.

Mitochondrial Genome-Encoded Long Noncoding RNA Cytochrome B (LncCytB) and Mitochondrial Ribonucleases in Diabetic Retinopathy.

Hyperglycemia damages mitochondria and downregulates transcription of mtDNA-encoded genes and the long noncoding RNA LncCytB, causing mitochondrial genomic instability. The genes encoded by mtDNA are transcribed as large polycistronic transcripts, and the 5' ends of precursor tRNAs are processed by mitochondrial-targeted ribonuclease P (MRPPs). Our aim was to investigate the role of MRPP1 in the downregulation of LncCytB in diabetic retinopathy. Using human retinal endothelial cells incubated in 20 mM D-glucose for 96 h, the gene expression and mitochondrial localization (immunofluorescence) of MRPP1 and the interaction between MRPP1 and LncCytB (determined by RNA-FISH and RNA immunoprecipitation) were quantified. The results were confirmed in retinal microvessels from streptozotocin-induced diabetic mice and from human donors with documented diabetic retinopathy. Compared to normal glucose, high glucose decreased mRNA and mitochondrial localization of MRPP1 and its interaction with LncCytB. While MRPP1 overexpression prevented glucose-induced decrease in MRPP1-LncCytB interaction, LncCytB expression and mitochondrial damage (reduction in protective nucleoids in mtDNA), MRPP1-siRNA further worsened them. Similar results were obtained from retinal microvessels from diabetic mice and from human donors with diabetic retinopathy. Downregulation of MRPP1 in diabetes suppresses LncCytB transcription, resulting in mitochondrial functional and genomic instability, ultimately leading to the development of diabetic retinopathy. Thus, preventing MRPP1 downregulation has the potential to inhibit retinopathy and prevent the fear of vision loss in diabetic patients.