Treatment-requiring Retinopathy Of Prematurity Research Articles

Multi-risk factors joint prediction model for risk prediction of retinopathy of prematurity

PurposeRetinopathy of prematurity (ROP) is a retinal vascular proliferative disease common in low birth weight and premature infants and is one of the main causes of blindness in children.In the context of predictive, preventive and personalized medicine (PPPM/3PM), early screening, identification and treatment of ROP will directly contribute to improve patients’ long-term visual prognosis and reduce the risk of blindness. Thus, our objective is to establish an artificial intelligence (AI) algorithm combined with clinical demographics to create a risk model for ROP including treatment-requiring retinopathy of prematurity (TR-ROP) infants.MethodsA total of 22,569 infants who underwent routine ROP screening in Shenzhen Eye Hospital from March 2003 to September 2023 were collected, including 3335 infants with ROP and 1234 infants with TR-ROP among ROP infants. Two machine learning methods of logistic regression and decision tree and a deep learning method of multi-layer perceptron were trained by using the relevant combination of risk factors such as birth weight (BW), gestational age (GA), gender, whether multiple births (MB) and mode of delivery (MD) to achieve the risk prediction of ROP and TR-ROP. We used five evaluation metrics to evaluate the performance of the risk prediction model. The area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) were the main measurement metrics.ResultsIn the risk prediction for ROP, the BW + GA demonstrated the optimal performance (mean ± SD, AUCPR: 0.4849 ± 0.0175, AUC: 0.8124 ± 0.0033). In the risk prediction of TR-ROP, reasonable performance can be achieved by using GA + BW + Gender + MD + MB (AUCPR: 0.2713 ± 0.0214, AUC: 0.8328 ± 0.0088).ConclusionsCombining risk factors with AI in screening programs for ROP could achieve risk prediction of ROP and TR-ROP, detect TR-ROP earlier and reduce the number of ROP examinations and unnecessary physiological stress in low-risk infants. Therefore, combining ROP-related biometric information with AI is a cost-effective strategy for predictive diagnostic, targeted prevention, and personalization of medical services in early screening and treatment of ROP.

Retinopathy of prematurity in triplets - Indian twin city ROP study report number 12.

To evaluate the incidence and severity of retinopathy of prematurity (ROP) amongst surviving triplets. Records of preterm babies born to mothers with triplet pregnancies were retrieved from our Indian twin city ROP study database between 1 Jan 2000 and 31 Dec 2020 and analyzed. 253 surviving triplet babies born to 108 mothers were evaluated. 48 out of 108 (44%) mothers received treatment for infertility. Data was available and analyzed for 242 babies (484 eyes). Mean gestational age was 31.76 ± 3.74 weeks (26- 38 weeks). The mean birth weight was 1.44 ± 0.37 kg (0.57-2.76 kg). At the first screening, incomplete vascularization was noted in 67% (131 babies;322 eyes) of which ROP was diagnosed in 14% (28 babies; 56 eyes). Among them, only 18 babies (53%) were the smallest birth weight babies in each of the triplet sets. Treatment with laser or bevacizumab was performed in 14 babies (5.8%), one eye of one baby additionally needed vitreoretinal surgical intervention. Good anatomical outcomes in terms of regression of ROP without sequelae were achieved in all babies. The present study reveals low incidence and favorable outcomes of ROP in triplet pregnancies in a large cohort of babies from a middle-income country. Our cohort did not show any difference in the treatment-requiring ROP among the larger or smaller birth weight babies of the same gestational age. In multiple pregnancies, gestational age remains a critical factor for ROP development; however, this does not necessitate modifying screening or treatment criteria in such triplet pregnancies.

Early Single-Examination Optical Coherence Tomography Biomarkers for Treatment-Requiring Retinopathy of Prematurity.

Optical coherence tomography (OCT) is an emerging adjunct imaging modality to evaluate retinopathy of prematurity (ROP). From an 11-year research database, we identify early OCT biomarkers that predict treatment-requiring ROP (TR-ROP). For preterm infants with acceptable OCT images at 32 ± 1weeks postmenstrual age (PMA), we extracted the following measures: total retina, inner retinal layer (IRL), and outer retinal layer (ORL) thicknesses at the fovea and the parafovea, inner nuclear layer (INL) and choroidal thickness, parafovea/fovea (P/F) ratio, and presence of macular edema. Using univariable and multivariable logistic regression models, we evaluated the association between retinal and choroidal OCT measurements at 32 ± 1weeks PMA and development of TR-ROP. Of 277 eyes (145 infants) with usable OCT images, 67 eyes had TR-ROP. Lower P/F ratio (P<0.0001), thicker foveal IRL (P=0.0001), and thinner choroid (P=0.03) were associated with TR-ROP in univariable analysis, but lost significance of association when adjusted for gestational age and race. Absence of macular edema was associated with TR-ROP when adjusted for gestational age and race (P=0.01). In 185 eyes without macular edema, P/F ratio was associated with TR-ROP in both univariable analysis (P<0.0001) and multivariable analysis (P=0.02) with adjustment for gestational age and race. Presence of macular edema at 32 ± 1weeks PMA in infants with lower gestational age may be protective against TR-ROP. In infants without macular edema, P/F ratio may be an early OCT biomarker for development of TR-ROP. Incorporation of early OCT biomarkers may be useful in prediction of TR-ROP.

Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort

Background/aimsWe assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO2), and developed a risk prediction model for severe ROP using birth data and SpO2...

Systemic exposure to aflibercept after intravitreal injection in premature neonates with retinopathy of prematurity: results from the FIREFLEYE randomized phase 3 study

BackgroundThere are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy of prematurity (ROP). FIREFLEYE compared aflibercept 0.4 mg/eye and laser photocoagulation in infants with acute-phase ROP requiring treatment.MethodsInfants (gestational age ≤32 weeks or birthweight ≤1500 g) with treatment-requiring ROP in ≥1 eye were randomized 2:1 to receive aflibercept 0.4 mg or laser photocoagulation at baseline in this 24-week, randomized, open-label, noninferiority, phase 3 study. Endpoints include concentrations of free and adjusted bound aflibercept in plasma, pharmacokinetic/pharmacodynamic exploration of systemic anti-vascular endothelial growth factor effects, and immunogenicity.ResultsOf 113 treated infants, 75 received aflibercept 0.4 mg per eye at baseline (mean chronological age: 10.4 weeks), mostly bilaterally (71 infants), and with 1 injection/eye (120/146 eyes). Concentrations of free aflibercept were highly variable, with maximum concentration at day 1, declining thereafter. Plasma concentrations of adjusted bound (pharmacologically inactive) aflibercept increased from day 1 to week 4, decreasing up to week 24. Six infants experienced treatment-emergent serious adverse events within 30 days of treatment; aflibercept concentrations were within the range observed in other infants. There was no pattern between free and adjusted bound aflibercept concentrations and blood pressure changes up to week 4. A low-titer (1:30), non-neutralizing, treatment-emergent anti-drug antibody response was reported in 1 infant, though was not clinically relevant.Conclusions24-week data suggest intravitreal aflibercept for treatment of acute-phase ROP is not associated with clinically relevant effects on blood pressure, further systemic adverse events, or immunogenicity.ClinicalTrials.gov IdentifierNCT04004208.

A pilot optical coherence tomography angiography classification of retinal neovascularization in retinopathy of prematurity

Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

Neurodevelopmental Outcomes in Infants Screened for Retinopathy of Prematurity

Preterm infants screened for retinopathy of prematurity (ROP) are at risk for heterogenous neurodevelopment outcomes that are difficult to predict. To characterize the potential association between socioeconomic and clinical risk factors and neurodevelopmental outcomes in a diverse, multicenter cohort of premature neonates screened for ROP. This was a retrospective cohort study using electronic medical records and US Census Bureau income data. This study was performed at academic (University of California, Los Angeles [UCLA] Mattel Children's Hospital and UCLA Santa Monica Hospital), community (Cedars-Sinai Medical Center), and LA county (Harbor-UCLA Medical Center) neonatal intensive care units. Participants included infants who met American Academy of Pediatrics guidelines for ROP screening and had records from at least 1 Bayley Scales of Infant and Toddler Development (BSID) neurodevelopment assessment between 0 and 36 months of adjusted age. Data analyses were conducted from January 1, 2011, to September 1, 2022. Demographic and clinical information, proxy household income, and health insurance type were collected as risk factors. Neurodevelopmental outcomes in the cognitive, language, and motor domains measured via BSID were the primary outcomes. A total of 706 infants (mean [SD] age, 28.6 [2.4] weeks; 375 male [53.1%]) met inclusion criteria. In a multivariable model, which included adjustments for birth weight, sex, insurance type, intraventricular hemorrhage (IVH), and age at assessment, public health insurance was associated with a 4-fold increased risk of moderate to severe neurodevelopmental impairment (NDI) in cognitive and language domains (cognitive, odds ratio [OR], 3.65; 95% CI, 2.28-5.86; P = 8.1 × 10-8; language, OR, 3.96; 95% CI, 2.61-6.02; P = 1.0 × 10-10) and a 3-fold increased risk in the motor domain (motor, OR, 2.60; 95% CI, 1.59-4.24; P = 1.4 × 10-4). In this adjusted model, clinical factors that were associated with an increased risk of moderate to severe NDI included lower birth weight, diagnosis of IVH, male sex, and older age at time of Bayley assessment. In unadjusted analyses, infants who received either laser or anti-VEGF treatment, compared with infants without treatment-requiring ROP, had lower BSID scores in multiple domains at 0 to 12 months, 12 to 24 months, and 24 to 36 months (DATA). In the multivariable model, treatment type was no longer associated with worse neurodevelopmental outcomes in any domain. Study results suggest an association between public insurance type and NDI in a diverse population screened for ROP, indicating the complexities of neurodevelopment. This study also supports the early neurodevelopmental safety of anti-VEGF treatment, as anti-VEGF therapy was not found to be independently associated with worse NDI in any domain.

Refractive errors in infants with retinopathy of prematurity treated using laser or anti-vascular endothelial growth factor monotherapy

Background: Infants treated for retinopathy of prematurity (ROP) could develop visually significant refractive errors. In this study, we report pre-treatment refractive errors in premature infants with treatment-requiring ROP treated using laser or anti-VEGF monotherapy and compare the components of post-treatment refractive error values between the two treatment groups at different follow-up timepoints.&#x0D; Methods: In this retrospective cohort study, we analyzed 360 eyes of 181 premature infants with treatment-requiring ROP who were referred to Farabi Eye Hospital, Tehran, Iran between March 2020 and April 2021. Of the 360 eyes, 195 received laser monotherapy (laser treatment group) and 165 received an intravitreal anti-VEGF injection (anti-VEGF therapy group). All included eyes underwent pre- and post-treatment cycloplegic refraction. Cycloplegia was induced for each infant by instilling a mixed eye drop containing 1% tropicamide, 2.5% phenylephrine, and 0.5% tetracaine (in equal volumes) in each eye three times at five-minute intervals. Cycloplegic refraction was performed 30 minutes after the third instillation.&#x0D; Results: The mean (standard deviation [SD]) gestational age (GA) and birth weight (BW) of the infants were 29.0 (2.0) weeks and 1241.0 (403.0) g, respectively. The male-to-female ratio in the entire study cohort was 107 (59.1%) / 74 (40.9%), whereas the ratios in the anti-VEGF therapy group and laser treatment group were 47 (56.6%) / 36 (43.4%) and 60 (61.2%) / 38 (38.8%), respectively. The pre-treatment assessment revealed that 218 (60.6%) eyes were hyperopic, 112 (31.1%) were myopic, and 30 (8.3%) were emmetropic. In the anti-VEGF therapy group, 87 (52.7%) eyes were hyperopic, 63 (38.2%) were myopic, and 15 (9.1%) were emmetropic. In the laser treatment group, 131 (67.2%) eyes were hyperopic, 49 (25.1%) were myopic, and 15 (7.7%) were emmetropic. The mean (SD) spherical refractive error and spherical equivalent of refractive error (SEQ) at the 1-week, 1-month, and &gt; 6-month post-treatment follow-up timepoints; the mean cylindrical refractive error at the 3-month post-treatment timepoint; and the mean SEQ at the time of ROP regression were significantly different between the treatment groups (all P &lt; 0.05). The rate of anisometropia increased significantly from 3.4% at baseline to 9.2% at the 6-month post-treatment follow-up timepoint (P &lt; 0.05).&#x0D; Conclusions: In this study, the most common pre-treatment refractive status of all included eyes with treatment-requiring ROP and eyes in each treatment group was hyperopia, followed by myopia and emmetropia. At the more than 6-month post-treatment follow-up, cycloplegic refraction revealed that the laser-treated eyes were significantly more hyperopic than the anti-VEGF-treated eyes, a finding similar to the pre-treatment refraction results. Further studies of same cohort with a longer follow-up period and a control group are needed to determine the real-world effect of each treatment modality on the refractive statuses of children treated for ROP.

Outcomes for non-treatment-requiring infants evaluated for retinopathy of prematurity

To evaluate the rates of visually significant disorders in patients without treatment-requiring retinopathy of prematurity (ROP) at initial follow-up after completion of ROP examinations. The medical records of all babies evaluated for retinopathy of prematurity between June 2015 and September 2020 were reviewed. Patients with documented gestational age, birth weight, and single versus multiple birth status who did not require ROP treatment and who followed-up with our institution's pediatric ophthalmologist were included. A total of 304 patients were included. Of these, 15 (4.9%) had strabismus (12 [4.0%] with esotropia, 3 [0.9%] with exotropia), 30 (9.9%) had myopia, 174 (57.2%) had hyperopia, 54 (18%) had astigmatism, 4 (1.3%) had amblyopia, 5 (1.6%) were labeled amblyopia suspects, 1 (0.3%) had congenital glaucoma, and 1 (0.3%) had congenital cataract. Nineteen (6.3%) had a condition requiring intervention at the first evaluation following completion of ROP examinations, and in 5 (2%), this was a condition that would typically not have been identified without evaluation by a pediatric ophthalmologist. In our population of infants evaluated for retinopathy of prematurity who did not require ROP treatment, the incidence of other ocular disorders requiring intervention at the first non-ROP evaluation was about 6%. This study highlights the need for further research that may aid in the creation of an evidence-based follow-up strategy for premature infants who never undergo ROP treatment.

Identification and clinical significance of tsRNAs and miRNAs in PBMCs of treatment-requiring retinopathy of prematurity

The aim of the study is to reveal the expression profiling and clinical significance of peripheral blood mononuclear cell (PBMC) tRNA-derived small RNAs (tsRNAs) and microRNAs (miRNAs) of premature infants with treatment-requiring retinopathy of prematurity (ROP). Significantly altered tsRNAs and miRNAs were screened using small RNA sequencing. RT-qPCR was used to verify the altered RNAs identified by small RNA transcriptomics. The target genes, their enriched functions, and possibly involved signaling pathways were identified by bioinformatics analyses. According to the small RNA sequencing, 125 tsRNAs and 205 miRNAs were significantly altered in PBMCs obtained from infants with treatment-requiring ROP compared with the premature controls without retinopathy. We preliminarily validated the significant alterations of 6 tsRNAs and 9 miRNAs. The target genes for those tsRNAs were enriched for cellular macromolecule metabolic process, intracellular anatomical structure, transcription regulatory region nucleic acid binding, and Th17 cell differentiation; those of the altered miRNAs were enriched for the developmental process, cell junction, DNA-binding transcription activator activity, and FoxO signaling pathway. By verification with the extended sample size, we identified tsRNAs and miRNAs that could be potential biomarkers with clinical values. The study recognized the alterations and clinical significance of changed tsRNA/miRNA profiles in PBMCs from premature infants with ROP. These significantly altered tsRNAs and miRNAs might be useful as potential diagnostic biomarkers and molecular targets for treatment-requiring ROP.

Epidemiologic Evaluation of Retinopathy of Prematurity Severity in a Large Telemedicine Program in India Using Artificial Intelligence

Epidemiological changes in retinopathy of prematurity (ROP) depend on neonatal care, neonatal mortality, and the ability to carefully titrate and monitor oxygen. We evaluate whether an artificial intelligence (AI) algorithm for assessing ROP severity in babies can be used to evaluate changes in disease epidemiology in babies from South India over a 5-year period. Retrospective cohort study. Babies (3093) screened for ROP at neonatal care units (NCUs) across the Aravind Eye Care System (AECS) in South India. Images and clinical data were collected as part of routine tele-ROP screening at the AECS in India over 2 time periods: August 2015 to October 2017 and March 2019 to December 2020. All babies in the original cohort were matched 1:3 by birthweight (BW) and gestational age (GA) with babies in the later cohort. We compared the proportion of eyes with moderate (type 2) or treatment-requiring (TR) ROP, and an AI-derived ROP vascular severity score (from retinal fundus images) at the initial tele-retinal screening exam for all babies in a district, VSS), in the 2 time periods. Differences in the proportions of type 2 or worse and TR-ROP cases, and VSS between time periods. Among BW and GA matched babies, the proportion [95% confidence interval {CI}] of babies with type 2 or worse and TR-ROP decreased from 60.9% [53.8%-67.7%] to 17.1% [14.0%-20.5%] (P < 0.001) and 16.8% [11.9%-22.7%] to 5.1% [3.4%-7.3%] (P < 0.001), over the 2 time periods. Similarly, the median [interquartile range] VSS in the population decreased from 2.9 [1.2] to 2.4 [1.8] (P < 0.001). In South India, over a 5-year period, the proportion of babies developing moderate to severe ROP has dropped significantly for babies at similar demographic risk, strongly suggesting improvements in primary prevention of ROP. These results suggest that AI-based assessment of ROP severity may be a useful epidemiologic tool to evaluate temporal changes in ROP epidemiology. Proprietary or commercial disclosure may be found after the references.

Automated detection for Retinopathy of Prematurity with knowledge distilling from multi-stream fusion network

Retinopathy of Prematurity (ROP) is a potentially blinding eye disease that primarily occurs in premature infants with low birth weight. It is the main cause of childhood blindness worldwide. Various methods are available for the staging of ROP detection. However, relatively few research has focused on the early-stage detection of ROP and Treatment-Requiring ROP (TR-ROP). Besides, most of the networks proposed in recent research contain tremendous neural network parameters. This study aimed to propose a lightweight TR-ROP detection neural network with knowledge distilling from a multi-stream fusion neural network based on early-stage fundus images. A multi-stream fusion neural network was first trained with high accuracy, then knowledge distillation was used to transfer knowledge from it to a lighter model to be suitable for deployment into an embedded ROP detection device. Experiments were conducted by using a five-fold cross-validation with a dataset consisting entirely of early-stage fundus images. The proposed network could achieve promising results, with accuracy, sensitivity, and specificity of 0.9734, 0.9456, and 0.9823, in ROP detection, and 0.9222, 0.9516, and 0.8571, in TR-ROP detection, which is superior to the existing state-of-the-art methods.

Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response.

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.

Tailoring Screening Guidelines for Retinopathy of Prematurity in Egypt: An Exploratory Multicentric Study.

Retinopathy of prematurity (ROP) is increasing in incidence in developing nations, including Egypt. Secondary prevention requires timely detection through the development of regional screening guidelines, which should be preceded by large-scale studies to characterize the population at risk. A prospective, multicentric exploratory study that included five large tertiary institutions in an urban Egyptian setting. All infants born with gestational age (GA) < 37 weeks and/or birth weight (BW) ≤ 2000 grams were screened. More mature and heavier infants with unstable clinical course were also included. The primary outcome measure was the rate of ROP and high-risk disease occurrence in relation to underlying risk factors. Of the 768 eyes (384 screened infants), 347 eyes (45.2%) had stage 1 or higher disease, and 43 eyes (5.6%) had high-risk disease. Eyes with stage 1 or higher ROP and treatment-requiring ROP had a mean (± SD) GA of 33.4 (± 2.6) weeks and 32.8 (± 3.2) weeks, and BW of 1842.3 (± 570.1) grams and 1747.6 ± (676.2) grams, respectively. Treatment-requiring eyes belonged to infants that had significantly lower GA and significantly higher prevalence of co-morbidities than non-treatment-requiring eyes. The incidence of ROP and high-risk disease in an urban Egyptian setting are similar to those in comparable settings elsewhere and locally. This exploratory study supports tailoring local screening criteria for ROP, and may aid the future development of national guidelines.

G-ROP criteria for predicting retinopathy of prematurity among neonates with different birth weight percentiles

The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that adding postnatal weight gain to birth weight and gestational age detected 100% of cases with type 1 retinopathy of prematurity (ROP) while reducing the ROP examinations by 30%. The purpose of this study was to investigate whether being small for gestational age (SGA) affects the sensitivity and specificity of the G-ROP model. We applied the G-ROP criteria for premature infants. The infants were classified as three subgroups: SGA, appropriate for gestational age (AGA), and large for gestational age (LGA). The performance of G-ROP criteria was assessed for each group for ROP. There were 41 (10.5%) SGA, 312 (80%) AGA, and 37 (9.5%) LGA neonates. Twenty-six (6.7%) neonates were treated for ROP, and the G-ROP model identified all of them. The sensitivity of the model for treatment-requiring ROP (TR-ROP) was found to be 100% in the whole patient group and for each subgroup. The specificity for TR-ROP was 46.4% for the whole group, 50% for SGA, 44% for AGA, and 63.6% for LGA. By applying the G-ROP model, the number of ROP examinations could be reduced by 25% for the whole group, 27% for SGA, 24% for AGA, and 31% for LGA, without missing TR-ROP. The sensitivity and specificity of the G-ROP model for TR-ROP in SGA infants were similar to the whole group. The model did not miss any cases of TR-ROP.

Characterization of Errors in Retinopathy of Prematurity Diagnosis by Ophthalmologists-in-Training in Middle-Income Countries.

To characterize common errors in the diagnosis of retinopathy of prematurity (ROP) among ophthalmologistsin-training in middle-income countries. In this prospective cohort study, 200 ophthalmologists-in-training from programs in Brazil, Mexico, and the Philippines participated. A secure web-based educational system was developed using a repository of more than 2,500 unique image sets of ROP, and a reference standard diagnosis was established by combining the clinical diagnosis and the image-based diagnosis by multiple experts. Twenty web-based cases of wide-field retinal images were presented, and ophthalmologists-in-training were asked to diagnose plus disease, zone, stage, and category for each eye. Trainees' responses were compared to the consensus reference standard diagnosis. Main outcome measures were frequency and types of diagnostic errors were analyzed. The error rate in the diagnosis of any category of ROP was between 48% and 59% for all countries. The error rate in identifying type 2 or pre-plus disease was 77%, with a tendency for overdiagnosis (27% underdiagnosis vs 50% overdiagnosis; mean difference: 23.4; 95% CI: 12.1 to 34.7; P = .005). Misdiagnosis of treatment-requiring ROP as type 2 ROP was most commonly associated with incorrectly identifying plus disease (plus disease error rate = 18% with correct category diagnosis vs 69% when misdiagnosed; mean difference: 51.0; 95% CI: 49.3 to 52.7; P = .003). Ophthalmologists-in-training from middle-income countries misdiagnosed ROP more than half of the time. Identification of plus disease was the salient factor leading to incorrect diagnosis. These findings emphasize the need for improved access to ROP education to improve competency in diagnosis among ophthalmologists-in-training in middle-income countries. [J Pediatr Ophthalmol Strabismus. 2023;60(5):344-352.].

Association Between Retinopathy of Prematurity in Very-Low-Birth-Weight Infants and Neurodevelopmental Impairment

To evaluate the impact of retinopathy of prematurity (ROP) severity and the treatment of very-low-birth-weight infants (VLBWIs) on neurodevelopmental impairment in early childhood. Prospective cohort study. This was a prospective cohort study. The data were obtained from the Korean Neonatal Network (KNN), a nationwide registry for VLBWIs. Infants who were born from 2013 to 2015 and underwent ROP evaluation at birth and neurodevelopmental examinations at corrected ages of 18 to 24 months were included in the study. Infants with a history of meningitis or severe congenital anomalies were excluded. The VLBWI patients were grouped into no ROP, no treatment-requiring ROP (non-TR-ROP), and treatment-requiring ROP (TR-ROP) groups. Neurodevelopmental impairment was defined as participants who had at least 1 developmental problem according to the Bayley Scales of Infant and Toddler Development-2nd Edition (Bayley-II; <70), Bayley Scales of Infant and Toddler Development-3rd Edition (Bayley-III; <70), and Korean Developmental Screening Test (K-DST) tests (below -1 SD), and the Korean Ages and Stages Questionnaire (K-ASQ) (below the threshold) and Gross Motor Function Classification System (GMFCS; at level 2 or above). Multivariable logistic regression analysis was performed to evaluate the association between ROP and neurodevelopmental impairment. Among 3132 infants, 1093 (34.9%) had ROP. Among the ROP infants, 644 were not treated for ROP (non-TR-ROP group) and 449 received ROP treatments (TR-ROP group). The patients in the TR-ROP group had an increased risk of developing neurodevelopmental problems compared to those in the no ROP group (odds ratio [OR]=1.72, 95% CI=1.33-2.21). The TR-ROP group had a higher risk of all 3 types of neurodevelopmental problems: mental (OR=1.62, 95% CI=1.25-2.09), social (OR=1.62, 95% CI=1.12-2.09), and motor (OR=1.69, 95% CI=1.31-2.18). The risk of neurodevelopmental problems in patients treated with laser therapy did not differ from that in patients treated with anti-vascular endothelial growth factor (anti-VEGF) therapy (OR=1.17, 95% CI=0.73-1.88). ROP was independently associated with neurodevelopmental impairment in early childhood. The type of ROP treatment (anti-VEGF or laser treatment) did not affect neurodevelopmental impairment in patients in the TR-ROP group.

Potential biomarkers for retinopathy of prematurity identified by circular RNA profiling in peripheral blood mononuclear cells.

PurposeThis study aims to reveal the altered expression profiles of circular RNAs (circRNAs) in the peripheral blood mononuclear cells (PBMCs) of patients with retinopathy of prematurity (ROP), and to identify potential biomarkers for ROP diagnosis.MethodsDifferentially expressed circRNAs in PBMCs of five infants with ROP and five controls were identified using microarray analysis. Twelve altered circRNAs were validated using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Bioinformatic analyses were conducted to predict the circRNA/miRNA interactions, competing endogenous RNA (ceRNA) network, related biological functions, and signaling pathways. Four selected circRNAs in PBMCs were verified using RT-qPCR in another cohort, including 24 infants with ROP and 23 premature controls, and receiver operating characteristic (ROC) curves were used to estimate their potential as diagnostic biomarkers of ROP.ResultsA total of 54 and 143 circRNAs were significantly up- and down-regulated, respectively, in the PBMCs of patients with ROP compared with controls. Twelve of the significantly altered circRNAs were preliminarily validated by RT-qPCR, which confirmed the reliability of the microarray analysis. The circRNA/miRNA interactions and ceRNA network were displayed according to the altered circRNAs. Three circRNAs (hsa_circRNA_061346, hsa_circRNA_092369, and hsa_circRNA_103554) were identified as potential diagnostic biomarkers for ROP with certain clinical values.ConclusionsCircRNAs were significantly altered in PBMCs of treatment-requiring ROP patients. CircRNAs may be used as potential biomarkers and possible therapeutic targets for ROP.

The role of hepatic and renal functions in the development of retinopathy of prematurity: Is proteinuria a new risk factor?

To investigate the association of hepatic and renal parameters with the development of retinopathy of prematurity (ROP) in premature infants with a gestational age ≤ 32weeks. Medical records of 240 preterm infants were reviewed retrospectively, 85 of them were grouped as type 1, type 2 ROP, and control group. The 4th week hepatic and renal function test results of the groups, on the day of their first ROP examinations, were compared for the risk of development of ROP and the development of type 1 ROP. In this study, 12, 35, and 38 infants were enrolled in the type 1, type 2 ROP, and control group, respectively. The average gestational age and birth weight were higher; however, the duration of oxygen treatment was lower in the control group (p < 0.001). The blood glucose level was significantly higher in the type 1 ROP group than in the other groups (p = 0.023). The mean of total serum bilirubin of the type 1 ROP group was significantly lower than those of the type 2 ROP and control group (p = 0.032). Proteinuria was present in 85.7% of preterms with treatment-requiring ROP and proteinuria increased the risk of ROP by 3.9 times (OR with 95% CI 3.9 (1.19-12.75), p = 0.042). We found significantly higher blood glucose and lower total bilirubin level in the type 1 ROP group. Moreover, our findings suggest that proteinuria may not be only a comorbidity factor but also related to a higher frequency of ROP and type 1 ROP in preterm infants.

Evaluation of artificial intelligence-based retinopathy of prematurity screening in South India

Artificial intelligence (AI) based retinopathy of prematurity (ROP) screening has shown promise in India, but there remains a gap in knowledge as to how to implement AI, and how well it would perform against the clinical diagnosis of treatment-requiring (TR) ROP. The purpose of this paper was to evaluate the performance of the i-ROP DL algorithm, and a vascular severity score (VSS) against clinical diagnosis of treatment-requiring (TR) ROP in the Aravind Eye Hospital (AEH) network.