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Background: To explore the role of gut microbiota in preterm infants at high risk of developing retinopathy of prematurity (ROP)., Methods: Preterm infants with gestational age (GA) < 32 weeks and/or birth weight (BW) < 1500 g born between 2020 and 2021 were prospectively enrolled. Their faecal samples were collected and analysed at different postnatal ages of life using 16S rRNA gene sequencing on the Miseq platform. The main outcome measures were the microbial diversity, taxonomy, relative abundance, bacterial predicted functional analysis, and their associations with different ROP groups. Subgroup analyses were performed by matching their GA and BW across different ROP groups., Results: A total of 268 stool samples were collected from 110 preterm infants, including 13 with type 1 ROP, 44 with type 2 or mild ROP, and 53 without ROP. Type 1 ROP showed no significant difference in microbial diversity up to 8 postnatal weeks (p = 0.057), while type 2 and no ROP groups displayed increased diversity (p = 0.0015 and p = 0.049, respectively). Bifidobacterium genera was notably less abundant in type 1 ROP group at first postnatal week (p = 0.022) and remained low in subsequent weeks. Predicted functional analysis revealed enriched pathways in membrane transport, carbohydrate metabolism, amino acid metabolism, and replication and repair., Conclusions: Reduced gut microbial diversity may be associated with ROP development in high-risk preterm infants. Further research is needed to comprehend how early-life Bifidobacterium reduction affects metabolism and how targeting microbiome may help for ROP prevention and management., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Background/aims: The aims of this study is to evaluate the anatomic, visual outcomes and associated prognostic factors in patients with advanced retinopathy of prematurity (ROP) following vitrectomy., Methods: A retrospective cohort study of patients with ROP who underwent vitrectomy from 2005 to 2016 was conducted. All the patients had a follow-up period of at least 5 years. Univariate and multivariable logistic regression analyses were used to explore the factors related to unfavourable outcomes., Results: In total, 81 eyes of 51 patients were included. The mean age at last follow-up was 10.2 years. The anatomic success rate was 96.3% (26/27) for stage 4A, 90.9% (20/22) for stage 4B and 31.3% (10/32) for stage 5 ROP (p<0.01). The mean logMAR best corrected visual acuity of the stage-4A eyes was the highest, followed by those of stage-4B and stage-5 eyes (0.8, 1.5 and 2.6 for stages 4A, 4B and 5, respectively; p<0.01). High myopia (≤ -5.0 D) was noted in 70.8% and 71.4% of stage-4A and stage-4B eyes, respectively. Cataract was the most common complication (25.9%), followed by corneal opacity (17.3%), strabismus (16.1%), and phthisis (16.1%). Stage of the disease was a poor prognostic factor in all vitrectomised eyes (p<0.01). Vitrectomy combined lensectomy was a significant predictor for poor anatomic outcomes for stage-4 eyes (p=0.03). Presence of plus disease was also a possible factor affecting the surgical outcomes., Conclusion: The long-term surgical outcomes of the eyes with stage 4A and 4B ROP were favourable. Management of stage 5 ROP remained challenging., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Purpose: Determine whether intravitreal injection of bevacizumab exerts long-term effects on neurodevelopmental outcomes in children with retinopathy of prematurity (ROP) when reaching the age of 8 years., Methods: In total, 277 children were enrolled. Patients were stratified into full-term, preterm without ROP, ROP without treatment, or ROP with treatment groups, based on gestational age and ROP status. Children under the gestational age of 37 weeks were considered premature. Patients' cognitive outcomes were evaluated using a full-scale intelligence quotient (full score and percentile) generated by the Wechsler Intelligence Scale for Children-Fourth Edition every 1 year to 2 years., Results: At the mean age of 7.8 years, ROP without and with treatment groups demonstrated lower full-scale intelligence quotient scores and percentiles, compared with full-term and premature groups (both P < 0.05). Full-scale intelligence quotient scores and percentiles did not significantly differ between patients who received different treatments for ROP (full score P = 0.19; percentile P = 0.37). After adjusting for gestational age, logMAR best-corrected visual acuity was negatively associated with full-scale intelligence quotient scores ( P = 0.0008) and percentiles ( P = 0.0002)., Conclusion: At the mean age of 8 years, patients with ROP undergoing injection of bevacizumab did not exhibit worse cognitive outcomes than those who underwent laser photocoagulation or both treatments. Gestational age and best-corrected visual acuity correlated with cognitive development in children.

Purpose: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment., Methods: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed., Results: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3-5 years and 6-8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9-11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis., Conclusions: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate choroidal changes over time in school-age children with a history of prematurity., Methods: A study of 416 eyes of 208 eligible participants, including 88, 190, 36, 56, and 46 eyes in the full-term control, preterm, spontaneously regressed retinopathy of prematurity, intravitreal bevacizumab (injection of bevacizumab)-treated retinopathy of prematurity, and laser-treated retinopathy of prematurity groups, respectively, were enrolled in this study. The choroidal thickness was measured 4 times at 6-month intervals using optical coherence tomography., Results: Of all the groups, the laser-treated children had the thinnest choroid compared with full-term children (-52.3 µ m, P = 0.04). Preterm children exhibited greater attenuation in choroidal thickness over time than did full-term children (-6.3 ± 26.9 and -1.1 ± 12.8 µ m/year, P = 0.03), whereas no difference was observed between injection of bevacizumab and laser treatments (-4.6 ± 18.9 and -2.0 ± 15.7 µ m/year, P = 0.46). In all groups, the changes in axial length were negatively associated with the changes in choroidal thickness (all P < 0.05)., Conclusion: A greater attenuation in choroid thickness over time was observed in preterm children than in full-term children, but this attenuation did not differ between injection of bevacizumab and laser treatments. Axial elongation was associated with choroidal thinning in school-age children.

Purpose: The purpose of this study was to analyze human corneal endothelial cells (HCECs) morphology and ocular biometrics in premature (PM) children with or without retinopathy of prematurity (ROP)., Methods: Retrospective data on patient demographics, HCECs status, and ocular biometrics with at least 2 visits between 2016 and 2021 were reviewed. The main outcomes were endothelial cell density (ECD), coefficient of variation (CV), hexagonal cell ratio (HEX), central corneal thickness (CCT), axial length, anterior chamber depth, keratometry, corneal diameter, pupil diameter, and refraction status. Generalized estimating equation was used to evaluate the differences between PM no-ROP and ROP groups. We also analyzed the trend of ECD, CV, HEX, and CCT change with age between groups., Results: The study included 173 PM patients without ROP and 139 patients with ROP. A total of 666 and 544 measurements were recorded in the PM no-ROP and ROP groups, respectively. The ROP group had higher spherical power, myopic spherical equivalent (SE), and steeper steep keratometry (K; P < 0.05). The ROP group had higher CV (P = 0.0144), lower HEX (P = 0.0012) and thicker CCT (P = 0.0035). In the HCECs parameters, the ROP group had slower ECD decrement (P < 0.0001), faster CV decrement (P = 0.0060), and faster HEX increment (P = 0.0001). A difference in corneal morphology changes between the ROP and PM no-ROP groups were prominent in patients with lower gestational age (GA) in the subgroup analysis., Conclusions: Worse HCECs morphology and higher myopic status were initially observed in patients with prior ROP but not in PM patients with no-ROP. ECD and HCECs morphology improved with age, especially in patients with low GA.

Objectives: To evaluate respiratory outcomes in preterm infants with retinopathy of prematurity (ROP) following intravitreal bevacizumab injection (IVB)., Methods: This single-centre study enroled preterm infants with a gestational age (GA) < 34 weeks or a birth weight (BW) < 1500 g with bilateral type 1 ROP who received a single IVB, and a treatment-free control group matched by GA, postmenstrual age, and respiratory status at the time of the IVB. The primary outcome was serial respiratory changes in mean airway pressure (MAP), fraction of inspired oxygen (FiO 2 ), and respiratory severity score (RSS, MAP x FiO 2 ) during the 28-day post-IVB/matching period and overall respiratory improvement at day 28 and at discharge. The duration of supplemental oxygen therapy following IVB/matching was documented., Results: A total of 5578 infants were included. Seventy-eight infants were enroled in the IVB group, and another 78 infants were matched as the control group. Both groups had downward trends in the MAP, FiO 2 , and RSS over the study period (all P < 0.001), but there were no between-group differences in these measures. The percentage of overall respiratory improvement was similar between the IVB and control groups, so was the duration of invasive and in-hospital oxygen ventilation. A lower percentage of oxygen dependence at discharge in the IVB group (P = 0.03) remained significant after adjusting for GA and BW., Conclusions: This is a matched case study to evaluate respiratory outcomes in preterm infants following IVB for ROP. We found that the IVBs did not compromise respiratory outcomes in preterm infants during the 28-day post-IVB period and at discharge., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Objectives: To evaluate corneal topography in full-term and preterm children with or without retinopathy of prematurity (ROP)., Methods: We enrolled children aged from 2 years to 12 years between January 2019 and May 2021 in the following four groups: full-term (group 1), premature without ROP (group 2), untreated premature with ROP (group 3), and laser-treated and/or intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF)-treated premature with ROP (group 4). Corneal topography was measured with the Galilei Placido-dual Scheimpflug analyzer G4 every half year, and was compared among the groups using generalized estimating equation models at approximately 7 years of age., Results: We included 77, 178, 45, and 131 participants in groups 1, 2, 3, and 4, respectively. The mean (standard deviation) number of visits per patient was 2.9 (1.4). Compared with full-term eyes, premature eyes demonstrated steeper anterior corneal curvature (p = 0.016 and p = 0.008 for the mean and steep K, respectively), higher anterior and posterior corneal astigmatism (p = 0.036 and p = 0.016, respectively), and thinner thinnest pachymetry (p < 0.001). The laser-treated ROP eyes displayed steeper anterior corneal curvature (p = 0.040 for steep K) and higher anterior corneal astigmatism (p = 0.005) than the IVI-treated eyes. Moreover, they exhibited high cone location and magnitude index (1.96) reaching the cut-off for detecting keratoconus (1.82)., Conclusions: The premature status led to greater corneal ectasia, and laser treatment for ROP caused further corneal steepness. Higher anterior corneal astigmatism was associated with laser treatment. The ROP pathology and IVI anti-VEGF treatment exerted a marginal effect on corneal topography., (© 2023. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Purpose: This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk., Methods: Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics., Results: A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did., Conclusions: VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Purpose: To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP)., Design: Retrospective cohort study., Methods: This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months., Results: A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores., Conclusions: Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: To investigate late vitreoretinal complications and visual outcomes in patients with regressed retinopathy of prematurity (ROP) with or without prior treatment., Design: International, multicenter, noncomparative retrospective case series., Participants: We analyzed 264 eyes of 238 patients from 13 centers worldwide who developed vitreoretinal complications (retinal detachment [RD], vitreous hemorrhage [VH], or retinal break) ≥ 2 years after resolution of acute ROP., Methods: Each participant was assigned to 1 of 3 groups (the RD, VH, and retinal break groups) according to their primary diagnosis. The average age at presentation, visual acuities, refractive error, axial length, gestational age, birth weight, acute ROP classification, prior treatments for acute ROP, postoperative visual acuity (VA), and concomitant eye conditions in the 3 groups were documented and compared., Main Outcome Measures: Clinical features and visual outcomes of late vitreoretinal complications in patients with regressed ROP., Results: A total of 264 eyes of 238 patients were included. The prior acute ROP status was comparable among the 3 groups, except that the VH group had a higher proportion of patients with type 1 ROP (P = 0.03) and prior treatment (P < 0.001) than the other groups. The average age at presentation was earlier in the RD (20.3 ± 15.5 years) and VH (21.4 ± 18.9 years) groups than in the retinal break group (31.9 ± 18.2 years; P < 0.001). The retinal break group had the best presenting best-corrected VA, followed by the RD and VH groups (P < 0.001). Surgical intervention improved VA in both the RD and VH groups (both P < 0.05). The overall trend of VA was the most favorable in the retinal break group, followed by that in the VH and RD groups. Cicatricial changes in the fellow retina were observed in > 90% of patients with unilateral involvement., Conclusions: Infants with acute ROP remain at a high risk of vision-threatening complications throughout childhood and adulthood. Continual follow-up of patients with ROP is important. When severe complications, such as RD or VH, are detected, timely surgical intervention is necessary to ensure favorable visual outcomes in these patients., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

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.

Purpose: To compare between oral and intravenous (IV) ultrawide-field fluorescein angiography in pediatric patients with a history of prematurity of retinopathy or prematurity., Methods: Pediatric patients (<18 year old; n = 107 patients) who underwent ultrawide-field fluorescein angiography for retinopathy of prematurity were categorized into oral and IV fluorescein angiography (FA) groups. Quality of FA images was graded on the order of retinal vessels visible. Reported outcomes were proportions of graded FA images, peak fluorescein intensity, and the time to first dye appearance and to reach peak fluorescence., Results: Image quality analysis revealed that 91.5% of IV FA images had excellent image quality compared with only 55.6% of oral FA images (P < 0.01). There were still 83.3% of oral-contrast images with good or excellent image quality. The average time required for first dye appearance and peak fluorescence were significantly shorter in the IV FA group than in the oral FA group (P < 0.01). Peak intensity was greater in the IV group (141.41 ± 29.09) than in the oral group (111.25 ± 45.68; P < 0.01). Adverse reaction rates were similar between the two groups (P = 0.22)., Conclusion: Ultrawide-field fluorescein angiography provides excellent-quality imaging of the retina in the pediatric population. Overall, oral FA is still an effective and useful alternative to IV FA in children with prematurity history.

There has been limited research regarding the status of foveal hypoplasia and the characteristics of the optical components of the eye in patients with familial exudative vitreoretinopathy (FEVR) and retinopathy of prematurity (ROP). In this retrospective cohort study, patients were classified into five groups: patients with stage 1 and 2 FEVR (FEVR group), patients with ROP who received treatment (treated ROP group), patients with ROP who did not receive treatment (untreated ROP group), patients without ROP who had been born preterm (preterm group), and healthy patients who had been born at term (full-term group). Visual acuity, refractive error, characteristics of the optical components, and features of the fovea were compared. In total, 179 eyes from 100 patients were included. Patients in the FEVR group had the highest degrees of myopia (p < 0.001). The axial length of patients in the FEVR group was significantly longer than that of patients in the treated and untreated ROP, preterm, and full-term groups (p < 0.001, p < 0.001, p = 0.001, and p = 0.003, respectively). Patients in the FEVR group had a higher proportion of grade 4 foveal hypoplasia and thinner foveae than those in the other groups (p < 0.001). Patients with FEVR had significantly greater myopic change than patients with ROP; the significantly longer axial length of the FEVR group might be the reason for the greater myopic change and lesser macular thickness. Patients in the FEVR group had more foveal hypoplasia than those in the other groups., (© 2022. The Author(s).)

Purpose: To determine the long-term cognitive outcomes in children who underwent intravitreal bevacizumab (IVB) for retinopathy of prematurity (ROP)., Design: Prospective cohort study., Methods: This single-center study enrolled 186 children between 3 and 6 years of age and included 101 children in the final analysis: premature without ROP (group 1), ROP not needing treatment (group 2), IVB monotherapy (group 3), IVB plus laser therapy (group 4), and laser monotherapy (group 5). The Full-Scale Intelligence Quotient (FSIQ) was evaluated by the Wechsler Preschool and Primary Scale of Intelligence Test at baseline and then annually for 1-2 years and compared among groups., Results: The age at cognitive evaluation was 4.5-4.9 years at baseline and 6.1-7.0 years at the last follow-up. The FSIQ was comparable among the groups at both time points (P = .08 and .50, respectively). Severe cognitive impairment (FSIQ < 70) was more common in group 4 at baseline (4%, 22%, 13%, 33%, and 0% in groups 1-5, respectively; P = .03) but did not differ among the groups at the last follow-up (6%, 0%, 4%, 22%, and 0%; P = .22). After adjusting for sex, Apgar score, neonatal adverse events, and days on mechanical ventilation, IVB was not associated with FSIQ either at baseline or at the last follow-up., Conclusions: At 4.5 to beyond 6 years of age, children who underwent IVB monotherapy had comparable cognitive outcomes compared to the other premature children without prior IVB. Children who underwent IVB plus laser showed higher severe cognitive impairment at 4.5 years of age., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: To determine longitudinal differences in foveal thickness in preschool-aged patients with or without a history of type I retinopathy of prematurity (ROP)., Methods: A study of 201 eyes, including 32 laser±intravitreal bevacizumab (IVB)-treated eyes, 37 IVB-treated eyes, 14 spontaneously regressed ROP eyes, and 118 age-matched controls were enrolled in this study. The retinal thicknesses (full, inner and outer) were measured in the foveal area at 6-month intervals four consecutive times by optical coherence tomography., Results: The foveal thicknesses among the four groups were similar at all four visits (all p>0.05) after gestational age (GA) adjustment and remained similar with no differences after the full retinal thickness was divided into inner and outer thicknesses (all p>0.05). The full and outer foveal thicknesses of premature children increased over time (0.17 μm/month and 0.17 μm/month; p=0.0001 and 0.0003, respectively), but the inner foveal thickness remained unchanged with time (0.002 μm/month; p=0.09). Moreover, the positive correlation with best-corrected visual acuity was stronger for outer foveal thickness than for inner foveal thickness (γ=0.281, p<0.0001 and γ=0.181, p<0.0001, respectively)., Conclusion: The thickness of fovea in laser±IVB-treated, IVB-treated, regressed ROP and preterm eyes showed no difference after GA adjustment. The whole and outer foveal thicknesses increased with time in preschool-aged children over a 1.5-year follow-up period, but the inner foveal thickness remained unchanged with time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: To automatically detect and classify the early stages of retinopathy of prematurity (ROP) using a deep convolutional neural network (CNN)., Methods: This retrospective cross-sectional study was conducted in a referral medical centre in Taiwan. Only premature infants with no ROP, stage 1 ROP or stage 2 ROP were enrolled. Overall, 11 372 retinal fundus images were compiled and split into 10 235 images (90%) for training, 1137 (10%) for validation and 244 for testing. A deep CNN was implemented to classify images according to the ROP stage. Data were collected from December 17, 2013 to May 24, 2019 and analysed from December 2018 to January 2020. The metrics of sensitivity, specificity and area under the receiver operating characteristic curve were adopted to evaluate the performance of the algorithm relative to the reference standard diagnosis., Results: The model was trained using fivefold cross-validation, yielding an average accuracy of 99.93%±0.03 during training and 92.23%±1.39 during testing. The sensitivity and specificity scores of the model were 96.14%±0.87 and 95.95%±0.48, 91.82%±2.03 and 94.50%±0.71, and 89.81%±1.82 and 98.99%±0.40 when predicting no ROP versus ROP, stage 1 ROP versus no ROP and stage 2 ROP, and stage 2 ROP versus no ROP and stage 1 ROP, respectively., Conclusions: The proposed system can accurately differentiate among ROP early stages and has the potential to help ophthalmologists classify ROP at an early stage., Competing Interests: Competing interests: MFC is an unpaid member of the Scientific Advisory Board for Clarity Medical Systems (Pleasanton, California), a consultant for Novartis (Basel, Switzerland) and an initial member of Inteleretina (Honolulu, Hawaii). RVPC is on the Scientific Advisory Board for Visunex Medical Systems (Pleasanton, California) and a consultant for Genentech (South San Francisco, California). MFC and JPC receive research support from Genentech., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Vascular endothelial growth factor (VEGF) is the principal growth factor responsible for the retinal neovascularization in the pathogenesis of retinopathy of prematurity (ROP). Current therapies for ROP include laser ablation and intravitreal anti-VEGF injection. However, these treatments either destroy the peripheral retina or associate with problems of persistent peripheral avascular retina or later recurrence of ROP. In the present study we investigated a new therapeutic approach by exploring the potential role of a specific microRNA, miR-126, in regulating VEGFA expression and retinal neovascularization in a rat oxygen-induced retinopathy (OIR) model. We demonstrated that miR-126 mimic and plasmid effectively suppresses VEGFA mRNA expression in both human and rat retinal pigment epithelium cell lines, quantified with qRT-PCR. Animal experiments on rat OIR model revealed that intravitreal injection of miR-126 plasmid efficiently downregulated VEGFA expression in the intraocular fluid and retinal tissues measured by ELISA, and significantly suppressed retinal neovascularization, which was confirmed by calculating sizes of neovascularization areas on fluorescence microscopic images of flat mounted retina stained with Alexa Fluor 594-conjugated isolectin B4 to visualize blood vessels. Together, these results showed that intravitreal injection of miR-126 plasmid could inhibit retinal neovascularization by down-regulating VEGFA expression, suggesting a potential therapeutic effect for ROP., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the anatomical and functional outcomes of Type 1 retinopathy of prematurity 1 year after the intravitreal injection of aflibercept (IVA)., Methods: This prospective cohort study enrolled Type 1 retinopathy of prematurity patients who had been treated with IVA as first-line therapy from July 1, 2015, to June 30, 2017. Patients were followed up for at least 1 year after injection. The primary outcomes were retinopathy of prematurity regression, progression, reactivation, and the occurrence of associated complications after the use of IVA. The secondary outcomes were visual acuity and refractive error at 1 year after IVA., Results: Seventeen eyes of nine patients were enrolled in our study. A single IVA injection resulted in resolution in 15 eyes (88.2%), whereas 2 eyes (11.8%) needed retreatment. The mean Snellen visual acuity and refractive error were 6/13 ± 0.34 and -1.94 ± 2.97 D, respectively. No major ocular complications or systemic adverse effects were noted during the follow-up period, except one patient (11%) passed away at the age of 14 months due to a pulmonary infection., Conclusion: Aflibercept is effective and well tolerated for the treatment of Type 1 retinopathy of prematurity; it is a potential treatment option as it achieves good anatomical, visual, and refractive outcomes.

Aims: To construct a program to predict the visual acuity (VA), best corrected VA (BCVA) and spherical equivalent (SE) of patients with retinopathy of prematurity (ROP) from 3 to 12 years old after intravitreal injection (IVI) of anti-vascular endothelial growth factor and/or laser photocoagulation treatment., Methods: This retrospective study employed a feedforward artificial neural network with an error backpropagation learning algorithm to predict visual outcomes based on patient birth data, treatment received and age at follow-up. Patients were divided into two groups based on prior treatments. The main outcome measures were the difference between the predicted and actual values of visual outcomes. These were analysed using the normalised root mean square error (RMSE). Two-way repeated measures analysis of variance was used to compare the predictive accuracy by this algorithm., Results: A total of 60 ROP infants with prior treatments were included. In the IVI group, the normalised average RMSE for VA, BCVA, and SE was 0.272, 0.185 and 0.131, respectively. In the laser group, the normalised average RMSE for VA, BCVA and SE was 0.190, 0.250 and 0.104, respectively. This result shows that better predictive power was obtained for SE than for VA or BCVA in both the IVI and laser groups (p<0.001). In addition, the algorithm performed slightly better in predicting visual outcomes in the laser group (p<0.001)., Conclusions: This algorithm offers acceptable power for predicting visual outcomes in patients with ROP with prior treatment. Predictions of SE were more precise than predictions of for VA and BCVA in both groups., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To determine the rates and risk factors of recurrent retinopathy of prematurity (ROP) treated by laser photocoagulation, intravitreal bevacizumab (IVB) monotherapy, or intravitreal ranibizumab (IVR) monotherapy., Methods: In this retrospective cohort study, consecutive infants with Type 1 ROP who received laser, IVB, or IVR treatments were followed for at least 75 weeks of postmenstrual age. Data analysis was performed between March 2010 and February 2017 in Chang Gung Memorial Hospital, Linkou, Taiwan., Results: A total of 176 infants (340 eyes) were included in this study. The mean follow-up was 197.3 ± 110 weeks. All of the baseline demographic and ROP characteristics among the laser, IVB, and IVR groups were similar. The overall recurrence rate after treatment was 44 of 340 eyes (12.9%). The IVB group had a recurrence rate of 10.0%, followed by the laser group (18.0%) and the IVR group (20.8%); however, these rates were not significantly different (P = 0.0528). Compared with the laser group, the IVB and IVR groups exhibited recurrence at later ages (43.4 ± 3.5 weeks for the IVB group, 42.3 ± 2.0 weeks for the IVR group, and 39.5 ± 2.8 weeks for the laser group; P = 0.0058). The mean interval of recurrence from initial treatment in the laser group was 3.6 ± 1.4 weeks compared with 8.8 ± 3.9 weeks and 8.3 ± 1.6 weeks in the IVB and IVR groups, respectively (P = 0.0001). Overall, the independent risk factors of recurrence included an early postmenstrual age at initial treatment (P = 0.0160), Zone I (P = 0.0007), low Apgar score (P = 0.0297), and multiple births (P = 0.0285). There was no significant difference in progression to retinal detachment among the three groups (laser: 3/61, 4.9%; IVB: 2/231, 0.9%;and IVR: 1/48, 2.1%; P = 0.2701)., Conclusion: Laser, IVR, and IVB are effective for Type 1 ROP. Retinopathy of prematurity recurrence requiring re-treatment was encountered as late as 50 weeks of postmenstrual age after IVB or IVR but earlier after laser. Longer follow-up for infants treated with anti-vascular endothelial growth factor is needed, especially in patients with significant risk factors such as an early postmenstrual age at initial treatment, Zone I ROP, low Apgar score, and multiple births.

Purpose: To understand the epidemiology of retinopathy of prematurity (ROP) requiring treatment in Taiwan from 2002 to 2011., Methods: This retrospective cross-sectional study enrolled 11,180 premature patients with a length of stay >28 days who survived during hospitalization. The incidence of the first ROP treatment was analyzed., Results: Among ROP patients (n = 4,096), 6.5% (n = 265) received treatment. The most frequently performed treatment was laser administration (n = 199), followed by intravitreal anti-vascular endothelial growth factor (VEGF) injection (n = 38), scleral buckle or pars plana vitrectomy (n = 14), and cryotherapy (n = 14). The incidence of ROP requiring treatment increased during the study period, as did the use of intravitreal anti-VEGF injection. Shifts in the treatment modality from cryotherapy and scleral buckle/pars plana vitrectomy to laser treatment after 2003 and from laser treatment to intravitreal anti-VEGF injection after 2010 were observed., Conclusion: In Taiwan, the incidence of the use of intravitreal anti-VEGF injection for treating ROP increased between 2002 and 2011. Laser treatment was less frequently used than intravitreal anti-VEGF injection in 2011.

Purpose: To evaluate the neurodevelopmental and ocular developmental outcomes in premature children who have undergone intravitreal bevacizumab injection (IVB) for treatment of type 1 retinopathy of prematurity (ROP)., Design: Prospective case-control study., Participants: We enrolled 3 groups of premature patients: premature children who had no history of ROP (group 0), premature children with history of ROP without treatment (group 1), and premature children with ROP who had received a single IVB (0.625 mg; group 2)., Methods: Ocular developmental assessment, including cycloplegic refractometry, axial length, Cardiff acuity, and neurodevelopmental assessment via the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), were performed at 1 to 3 years of age and were compared between groups., Main Outcome Measures: Ocular developmental outcomes and Bayley III scores., Results: A total of 148 patients (85 boys and 63 girls) were included. The mean age at assessment was 1.49±0.59 years. Group 0 patients demonstrated significantly higher gestational age (GA), birth weight, and Apgar scores compared with group 1 and 2 patients. There were no significant differences between groups 1 and 2 in demographics or systemic risk factors except for lower GA in group 2. The cylindrical power was significantly larger in groups 1 and 2 compared with group 0. The spherical equivalent was significantly more myopic and the Cardiff acuity was significantly poorer in group 2 than in group 0. There were no significant differences between groups 1 and 2 in refractive status, axial length, or Cardiff acuity. Neurodevelopmental assessment using Bayley III showed no significant difference among the 3 groups in any aspect after adjusting for GA and other systemic risk factors. The risks for poor neurodevelopmental outcomes also were not significantly different., Conclusions: At the mean age of 1.5 years, children with prior history of IVB (group 2) showed similar refractive and visual outcomes and similar neurodevelopmental outcomes compared with premature patients with ROP without requirement of treatment (group 1), although there is a possibility that a small but clinically significant difference may not have been detected in the current study., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the macular structures, optical components, and visual acuity in preschool-aged children with a history of type I retinopathy of prematurity who underwent either intravitreal bevacizumab (IVB), laser, or a combination of treatments., Design: Comparative interventional case series., Methods: Setting: A referred medical center in Taiwan., Study Population: Eighty eyes from 42 patients (33 IVB-treated eyes from 17 children, 24 laser-treated eyes from 13 children, and 23 laser + IVB-treated eyes from 12 children)., Observation Procedure: Spectral-domain optical coherence tomography., Main Outcome Measures: The retinal thickness in the foveal area and the associated morphologic changes in foveal depression., Results: Compared with the laser-treated and laser + IVB-treated eyes, the IVB-treated eyes had less myopia and deeper anterior chamber depths but presented similar axial lengths and corneal curvatures (P = .001, P = .002, P = .95, and P = .16, respectively). The IVB-treated eyes had significantly thinner foveal, parafoveal, and perifoveal retinal thicknesses (P < .01 for all) and a higher incidence of foveal depression than the laser- or laser + IVB-treated eyes. The macular and subfoveal choroidal thicknesses did not differ among the groups (P = .21 and P = .63, respectively). Moreover, compared with the eyes treated with laser or laser + IVB, the IVB-treated eyes had better uncorrected visual acuity, although a significant difference was not observed in best-corrected visual acuity (P = .008 and P = .29, respectively)., Conclusions: Compared with laser therapy, IVB-treated eyes were associated with deeper anterior chamber depths and thinner foveal, parafoveal, and perifoveal thicknesses. Moreover, these IVB-treated eyes had fewer refractive errors and better uncorrected visual acuity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: To investigate the 10-year epidemiology and risk factors of retinopathy of prematurity (ROP) in Taiwan using the National Health Insurance Research Database., Methods: All premature infants (n = 34,192) from 2002 to 2011 were screened, and those with length of stay (LOS) longer than 28 days who survived after the initial discharge were enrolled (n = 11,180). The annual incidence of ROP and the risk factors associated with it were analyzed., Results: A total of 4096 ROP infants, 36.6% of premature babies with LOS longer than 28 days, were identified. The numbers of newborns, premature infants, and cases with ROP decreased over time, but the proportion of extremely low birth weight infants increased over time (P < 0.01 for test of trend in number). Also, the proportion of ROP infants receiving treatment increased over time (P < 0.01 for test of trend in number). However, the incidence of ROP was steady throughout the study period. Multivariable analysis revealed that low birth weight, male sex (odds ratio [OR] = 1.12, P = 0.007), and multiparity (OR = 1.17, P = 0.002) were positively associated with ROP, whereas necrotizing enterocolitis (OR = 0.72, P = 0.002) had a negative association with ROP., Conclusions: The average incidence of ROP from 2002 to 2011 in Taiwan showed no significant change over the 10-year period. Proportion of treatment-requiring ROP increased. Low birth weight, multiparity, and male sex were independent risk factors of ROP.

Background: To investigate the levels of VEGF in the systemic circulation of patients with type 1 ROP who received intravitreal injections of 1 mg (0.025 mL) aflibercept (IVA) or 0.625 mg (0.025 mL) bevacizumab (IVB)., Methods: Patients who had type 1 ROP and received either IVA or IVB were enrolled in this prospective study. Serum and plasma samples were collected prior to and up to 12 weeks after IVB or IVA treatment. The serum and plasma VEGF levels were measured using enzyme-linked immunosorbent assays (ELISAs), and the platelet levels in the blood were also quantified. The serum and plasma levels of VEGF, as well as the ratio of VEGF to platelet count (VEGF/PLT) were measured prior to and up to 12 weeks after anti-VEGF treatment., Results: In total, 14 patients with type 1 ROP were enrolled in this study; five patients received IVA, and nine patients received IVB. Following either IVA or IVB treatment, all the eyes (100%) showed complete resolution of ROP-induced abnormal neovascularization and presented continued vascularization toward the peripheral retina. Compared to baseline, the serum VEGF levels were significantly reduced in the ROP patients up to 12 weeks after either IVA or IVB treatments (all P < 0.05). At 2, 4, and 8 weeks after intravitreal injection, the serum VEGF levels were more suppressed in the IVB group than in the IVA group (P = 0.039, P = 0.004, and P = 0.003, respectively). The serum VEGF/PLT ratio after IVA or IVB showed similar reductions and trends as the serum VEGF data. Changes in the plasma VEGF levels could not be properly assessed because some of the samples had VEGF levels below the detection limit of the ELISA., Conclusions: Serum VEGF levels and the VEGF/PLT ratio in patients with type 1 ROP were suppressed for 3 months after treatment with either IVA or IVB, but the suppression of systemic VEGF was more pronounced in patients treated with IVB than those treated with IVA.

Purpose: To compare structural differences in the anterior chamber angle (ACA) and related optic components in children with or without retinopathy of prematurity (ROP)., Design: Prospective cross-sectional study., Methods: Setting: A referred medical center in Taiwan., Study Population: The patients included preterm children with a history of ROP who had undergone laser therapy. The controls included age-matched healthy full-term children., Observation Procedure: The ACA structures were evaluated using gonioscopy., Main Outcome Measures: The angularity of the anterior chamber and associated anatomic changes., Results: We examined 54 eyes of 29 preterm children with ROP and 134 eyes of 67 children born at term. The eyes of the ROP children exhibited a narrower ACA, steeper iris curvature, and more anteriorly inserted iris than those of the full-term children (P < .001, P = .002, and P = .08, respectively). The eyes of the ROP children also exhibited steeper corneas, shallower anterior chamber depths, thicker lenses, and higher degrees of refractive errors (all P < .001) than those of the full-term children. The axial lengths did not differ between the 2 groups (P = .15)., Conclusions: The eyes of the ROP children presented a narrower ACA and a more anteriorly curved and inserted iris than those of the full-term children. A steeper cornea, shallower anterior chamber, and greater lens thickness were the main structural changes in the anterior segment components of these patients. Further research is needed to investigate the association between these structural changes and the development of certain ocular diseases, such as glaucoma, in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To investigate vascular endothelial growth factor (VEGF) levels in the systemic circulation after intravitreal injections of bevacizumab (IVB) or ranibizumab (IVR) in patients with Type 1 retinopathy of prematurity (ROP)., Methods: Patients who had Type 1 ROP and received IVB or IVR were enrolled. Serum samples were collected before and up to 12 weeks after IVB or IVR treatment. The main outcome measurements were serum levels of VEGF up to 12 weeks after anti-VEGF treatment., Results: In total, 10 patients with Type 1 ROP were enrolled in this study. All the eyes had complete resolution of abnormal neovascularization of ROP after IVB or IVR. In the direct comparison of IVB with IVR, serum VEGF was found to be suppressed more in patients with Type 1 ROP who received IVB treatment, compared with those who received IVR treatment (P = 0.01, P = 0.03, and P = 0.03, respectively, 2, 4, and 8 weeks after intravitreal injection)., Conclusion: Serum VEGF levels in patients with Type 1 ROP were suppressed for 2 months after treatment with IVB, and VEGF levels were less affected after IVR treatment. Further studies are warranted to investigate the long-term effects of VEGF changes in ROP patients.

Background and Objective: To evaluate the surgical outcome of type 1 retinopathy of prematurity (ROP) after intravitreal ranibizumab (IVR) (Lucentis; Genentech, South San Francisco, CA) treatment., Patients and Methods: This was a prospective case series. Premature infants with treatment-requiring ROP who received IVR injections from 2013 to 2015 were included., Results: Twenty-two eyes of 12 children were included in the study. Complete resolution of ROP after a single IVR was noted in 73% of eyes. Retreatment was needed in 27% of eyes due to nonresponse to IVR (18%) or recurrence of ROP (9%). After that, all treated eyes (100%) demonstrated regressed ROP with attached retina. The median visual acuity was 0.3 LogMAR (range: 0 LogMAR to 0.8 LogMAR) with a mean follow-up of 25.2 months ± 6.8 months., Conclusions: IVR is effective and well-tolerated for patients with treatment-requiring ROP. However, nonresponse to IVR or recurrence of ROP after IVR was noted in 27% of treated eyes and required additional treatment. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1095-1105.]., (Copyright 2016, SLACK Incorporated.)

Purpose: To evaluate retinal anatomy and segmentation errors from spectral-domain optical coherence tomography (SD-OCT) imaging in school-aged children., Design: A prospective cohort study in a referral medical center., Methods: One hundred thirty-three eyes of 133 patients were enrolled. Patients were grouped as those who were treated for retinopathy of prematurity (ROP) (ROP-Tx group); those with spontaneously regressed ROP (ROP-non-Tx group); other premature patients (premature group); and full-term age-matched children (full-term group). Anatomy and segmentation errors of retina were evaluated by SD-OCT., Results: The mean age at assessment was 9.5 years (range, 4-16 years). The external limiting membrane (ELM) and the cone outer segment tips (COST) line were least frequently identified in patients of the ROP-Tx group (65.2% and 47.8%, P = .002 and P < .001, respectively). The visual acuity of the patients did not correlate significantly with the absence of COST line (P = .140) but correlated with the absence of ELM (P < .001). The presence of artifacts, including misidentification of the inner retina, misidentification of the outer retina, out-of-register artifacts, off-center scans, and degraded scan images, was observed to range from 0.6% to 50.0% in 4 groups of patients. All types of errors occurred more frequently in the ROP-Tx group than in the full-term group (all P < .05)., Conclusions: Outer retinal abnormalities were commonly observed in the ROP-Tx group. The higher segmentation errors in the ROP-Tx group might be related to fine structural abnormalities in the outer retina. Future studies are needed to investigate the mechanisms for these structural changes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years., Methods: The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development., Results: Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection., Conclusions: Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

Importance: Intravitreous injections of bevacizumab (IVB) have been found to be effective for the treatment of retinopathy of prematurity (ROP). However, serum levels of vascular endothelial growth factor (VEGF) have been found to be suppressed for 2 weeks after IVB in patients with ROP. Changes in serum VEGF levels after IVB in patients with ROP may be important because VEGF also plays a role in the neurodevelopment of newborns., Objective: To investigate the correlation of levels of VEGF and related growth factors with bevacizumab levels in the systemic circulation after IVB in patients with type 1 ROP., Design, Setting, and Participants: We studied a prospective case series at an institutional referral center from December 1, 2011, through February 28, 2013. We enrolled patients with type 1 ROP who received IVB. We collected blood samples before and for as long as 8 weeks after IVB. The samples were tested for serum levels of bevacizumab and growth factors, including VEGF, VEGF receptor 1 (VEGFR1), VEGFR2, Tie2, erythropoietin, transforming growth factor β1, insulinlike growth factor type 1, angiopoietin 1, angiopoietin 2, angiopoietinlike 3, and angiopoietin 4. The serum concentrations of these factors were measured using enzyme-linked immunosorbent assays., Main Outcomes and Measures: Serum levels of VEGF, bevacizumab, and the other growth factors before and for as long as 8 weeks after IVB., Results: We enrolled 8 patients with type 1 ROP. Bevacizumab levels were elevated 1 day after IVB in the 3 patients for whom measurements were available (mean [SD], 1425 [1010 (95% CI, 0-3934)] ng/mL; P = .13) and remained detectable in the serum as long as 8 weeks after IVB (285 ng/mL for the 1 patient with a measurement available). Serum VEGF levels were suppressed for the same period (mean [SD] level at 1 day after IVB, 379 [226 (95% CI, 190-568)] pg/mL for the 3 patients with measurements available; at 8 weeks, 216 pg/mL for the 1 patient with a measurement available). We found a negative correlation between the serum levels of bevacizumab and VEGF in the patients with ROP who received IVB (r = -0.43 [95% CI, -0.67 to -0.10]; P = .01). No changes were identified in the serum levels of any of the other factors after IVB. Bevacizumab may interfere with the actual level of VEGF in the serum, and the total VEGF level in the serum cannot be determined when bevacizumab is present. Wide CIs were noted in the measurement of these factors, probably owing to the small number of patients enrolled in this study., Conclusions and Relevance: Serum VEGF levels were suppressed for 2 months after IVB in patients with type 1 ROP owing to the leakage of bevacizumab into the systemic circulation.

Purpose: To investigate the 2-year outcomes of the natural history of retinopathy of prematurity (ROP) in Taiwan., Methods: A prospective study was conducted at two tertiary medical centers. Premature infants were screened and examined for ROP. The postmenstrual ages of developing each stage of ROP and the associated risk factors were recorded., Results: A total of 698 infants were included. The incidences of ROP and treatment-requiring ROP in all patients with ROP were 29.7% and 37.2%. When only including patients with birth weight of 1,250 g or less, the incidences were 62.2% and 39.1%, respectively. In patients with ROP with birth weight over 1,250 g, 25% of them developed treatment-requiring ROP. The median postmenstrual ages for the development of Stage 1, Stage 2, and Type 1 ROP were 33.0, 34.0, and 34.7 weeks, respectively. Gestational age at birth and birth weight were the most important factors associated with treatment-requiring ROP (hazard ratios of 0.3 and 0.6)., Conclusion: Our hospital-based study reveals an earlier postmenstrual age of developing ROP in this Asian population than in the Early Treatment for ROP study. Infants with birth weight over 1,250 g could still develop treatment-requiring ROP. Suboptimal oxygen control, different genetic dispositions among different races, inconsistencies in ROP diagnosis, and earlier screening might account for such a phenomenon.

Importance: The cause of reduced vision in patients with a history of retinopathy of prematurity (ROP) is not yet fully understood. The role of the choroid in ROP remains unknown and existing studies of choroidal thickness in patients with a history of ROP are limited. It might be helpful to understand the association of the choroid with ROP by measuring the choroidal thickness in patients with a history of ROP and correlating these findings with the visual outcome of these patients., Objective: To examine choroidal thickness by spectral-domain optical coherence tomography in children with a history of ROP and assess the impact of choroidal thickness on visual acuity., Design: A prospective cross-sectional analysis from August 2011 to September 2012., Setting: Institutional referral centers., Participants: Children aged 6 to 14 years with a history of ROP were classified into the following 2 groups: patients with a history of threshold ROP and treatment with laser or cryotherapy (treated group) and those with regressed ROP who had not received any treatment (nontreated group). All of the patients had a normal-appearing posterior pole., Intervention: Examinations of visual acuity, refractive errors, and optical components and measurement of choroidal thickness., Main Outcomes and Measures: Best-corrected visual acuity, optical components, and optical coherence tomography findings., Results: In total, 49 patients were enrolled in the study. Patients in the treated group had a significantly thinner choroidal thickness than the patients in the nontreated group after adjusting for age, axial length, and spherical power. Choroidal thickness was found to be positively associated with spherical power and spherical equivalent and negatively associated with axial length and vitreous depth. In addition, a thin choroidal thickness was associated with a worse best-corrected visual acuity., Conclusions and Relevance: Choroidal thickness is thinner in patients with threshold ROP compared with the patients with spontaneously regressed ROP. A thinner choroid is associated with worse vision in these patients. This study might imply the association of choroid circulation with ROP.

Background: To understand the characteristics, ophthalmic outcomes, and risk factors of retinopathy of prematurity (ROP) in patients with birth weight (BW) greater than 1500 g. The applicability of the ROP screening criteria to the Taiwanese population was also examined., Methods: The study included 104 eyes from 54 ROP patients who had BW greater than 1500 g from 1981 to 2008. Demographic information, disease courses, ophthalmic outcomes, and possible systemic risk factors were recorded. The infants were divided into groups of mild and severe ROP for a risk factor analysis., Results: The mean gestational age (GA) of the infants was 31 ± 1.3 weeks, and the mean BW was 1675 ± 249 g. Mild ROP regressed in 94 eyes (90%), and 10 eyes (10%) developed severe ROP. After various treatments, the regression rates for prethreshold or threshold ROP (n = 8) and stage 4 ROP (n = 2) were 100% and 50%, respectively. Forty-eight patients (85%) had at least three associated systemic risk factors. A multiple logistic regression analysis revealed that patients with an intraventricular hemorrhage were found to have an increased chance of developing severe ROP, especially those with BW greater than 1500 g (p = 0.015). There was also a significant association between patients who had severe ROP and an increased risk of having cerebral palsy (CP) at 1.5 years of age (p = 0.013)., Conclusion: The majority of patients with BW greater than 1500 g developed mild ROP. However, advanced ROP with poor visual outcome was also encountered in some patients.

Purpose: To investigate the effectiveness and complications associated with the use of bevacizumab, an anti-vascular endothelial growth factor agent, in the treatment of prethreshold retinopathy of prematurity (ROP)., Design: A multicenter, retrospective case series., Methods: Data from patients who had received intravitreal bevacizumab (IVB) injections for the treatment of ROP were collected from 4 medical centers in Taiwan. The main outcome measures were the regression of ROP and the complications that were associated with the IVB injections., Results: In total, 162 eyes from 85 patients were included in the study. After receiving IVB injections, 143 eyes (88%) exhibited ROP regression. Fourteen eyes (9%) required additional laser treatment for ROP regression after the absence of a positive response to the IVB injections. Three eyes (2%) progressed to stage 4 ROP and required vitrectomies to reattach the retinas. Two eyes (1%) received 1 additional IVB injection to decrease persistent plus disease. All of the eyes (100%) had attached retinas after the various treatments that they received. The major ocular complications that were associated with IVB injections included vitreous or preretinal hemorrhage in 2 eyes (1%); cataract in 1 eye (1%); and exotropia in 1 eye (1%). No notable systemic complications related to the IVB injections were observed., Conclusions: IVB injection seems to be an effective and well-tolerated method of treating prethreshold ROP. Laser therapy may still be required as a backup treatment for patients who do not respond to an IVB injection or for those in whom ROP worsens after an IVB injection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Purpose: To examine the optical components and spectral-domain optical coherence tomography (OCT) findings in children with a history of retinopathy of prematurity (ROP) and to identify any associations between the OCT findings and the visual acuities of the patients., Design: Prospective, case-controlled study., Participants and Controls: Children who were between 6 and 14 years of age were divided into the following 4 groups: Patients with a history of threshold ROP who had been treated using laser therapy or cryotherapy (group 1), patients with regressed ROP who had not received any treatment (group 2), patients who were born prematurely but who had no history of ROP (group 3), and normal full-term children (group 4). The posterior poles of the eyes of all of the patients seemed to be normal., Methods: Visual acuities, optical components, and macular thicknesses were measured in 4 groups of patients, and comparisons between the groups were made. Macular thicknesses were measured using OCT., Main Outcome Measures: Visual acuity (VA), optical components, and OCT findings., Results: We enrolled 133 patients in the study. Patients in group 1 had significantly thicker foveas than the other patients, as demonstrated by OCT, and this finding was negatively correlated with gestational age. The incidence of abnormal foveal contours among patients in group 1 was significantly higher than among the rest of the patients. Retention of the inner retinal layers was noted in group 1 patients; however, the structure of the outer retina remained intact. Greater degrees of myopic shift and astigmatism, steeper corneal curvatures, shallower anterior chamber depths, and thicker lenses were noted in previously treated ROP patients. These findings corresponded with poor VA and high refractive errors in group 1 patients., Conclusions: Patients with a history of threshold ROP are more likely to show abnormal foveal development and have a poorer visual prognosis than other patient groups despite a fundus with no macular dragging, disc dragging, or retinal detachment. A steeper corneal curvature, shallower anterior chamber, and greater lens thickness are the main changes in the optical components in these patients., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcome of a novel, modified 23-gauge vitrectomy system in the treatment of stage 4 retinal detachment in retinopathy of prematurity., Methods: Consecutive patients with stage 4 retinopathy of prematurity treated with modified 23-gauge vitrectomy were included in this medical record review. Major novel modifications included the use of a small infusion cannula, a 20-gauge blade for the creation of sclerotomies in the pars plicata, and a 23-gauge endoilluminator and vitreous cutter. Conjunctival dissection and suturing of sclerotomies were performed using this modified 3-port, 23-gauge vitrectomy technique. Anatomic success and surgical complications were analyzed., Results: Twenty-six eyes of 17 patients were included and analyzed. The mean (SD) gestational age was 28.0 (2.5) weeks, and the mean birth weight was 1199 (449) g. Mean postmenstrual age at the time of vitrectomy was 40.5 (3.0) weeks. Overall, 20 eyes (77%) achieved retinal attachment in a single operation, and 23 eyes (88%) achieved retinal attachment after multiple procedures. Postoperative complications included disc dragging (5 eyes [19%]), cataracts (4 [15%]), glaucoma (2 [8%]), persistent vitreous hemorrhage (1 [4%]), and posterior synechia (1 [4%])., Conclusions: This 23-gauge vitrectomy system seems to be a safe and effective approach for treatment of stage 4 retinopathy of prematurity. This modified system combines the benefits of 20- and 23-gauge vitrectomy and offers safer insertion of infusion cannulas in smaller eyes, more working space in pediatric eyes, a cutting port that is closer to the retina, and a faster cutting speed with less vitreous traction during the operation.

Purpose: To investigate the effects and complications of the anti-vascular endothelial growth factor agent bevacizumab in the treatment of retinopathy of prematurity (ROP) in Taiwanese patients., Design: A multicenter, retrospective case series study., Participants: Twenty-seven patients (49 eyes) from 4 medical centers across Taiwan., Methods: This study included patients receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) for the treatment of ROP between 2007 and 2009 at 4 major medical centers in Taiwan. The effects and complications associated with this treatment were analyzed. Patients were followed for at least 6 months after bevacizumab injection., Main Outcome Measures: Regression of ROP and the complications associated with the injection of bevacizumab., Results: Forty-nine eyes of 27 patients (18 male and 9 female) were included in the study. Mean gestational age and birth weight were 26.0 ± 2.4 weeks and 971.6 ± 589.6 g, respectively. There were 41 eyes (23 patients) with stage 3 ROP, 6 eyes (3 patients) with stage 4A ROP, and 2 eyes (1 patient) with stage 5 ROP. All of the eyes received only a single injection of IVB. The mean injection time was 36.8 ± 2.6 weeks postmenstrual age for eyes with stage 3 ROP. A total of 37 of 41 eyes (90%) with stage 3 ROP regressed after bevacizumab injection only. Four eyes (10%) required additional laser treatment to regress the ROP. Of 6 eyes (3 patients) with stage 4A ROP, 2 eyes (1 patient; 33%) regressed after bevacizumab injection and 4 eyes (67%) regressed after bevacizumab injection and subsequent vitrectomy. The 2 eyes with stage 5 ROP exhibited decreased vascular tortuosity after bevacizumab injection, but the retina failed to reattach after vitrectomy surgeries. Major complications included vitreous or pre-retinal hemorrhage in 4 eyes (8%) and transient vascular sheathing in 2 eyes (4%)., Conclusions: Bevacizumab injection seems effective and well tolerated in some cases of ROP, especially in stage 3 ROP. Ocular complications could result from the injection of bevacizumab in pediatric eyes., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the risk factors, especially maternal risk factors, associated with the development of retinopathy of prematurity (ROP) in premature babies., Methods: A matched case-control study involving premature patients was undertaken retrospectively. The case group consisted of premature babies with the subsequent development of ROP. The control group consisted of gestational age-matched and sex-matched premature babies that did not develop ROP during the follow-up period. Risk factors involving patient demographics and maternal characteristics were compared between the case and control groups., Results: A total of 144 patients were included in this study (72 patients in the case group and 72 patients in the control group). Among the 66 possible risk factors compared, only birth weight and maternal age were found to be significant risk factors. Birth weight was significantly lower in the case group (1,248.7 +/- 257.8 g vs. 1,335.5 +/- 297.2 g, P = 0.01), and maternal age was significantly older in the case group compared with that in the control group (31.2 +/- 5.1 years vs. 28.2 +/- 5.3 years, P < 0.001). The odds ratio of having babies with ROP was 2.9 when the maternal age was >30 years., Conclusion: Older maternal age is a newly identified risk factor for the development of ROP in premature babies.

Background: We report on the experience of retinopathy of prematurity (ROP) at Chang Gang Memorial Hospital (CGMH), Keelung, Taiwan over a 10-year period., Methods: A retrospective review was made of data of all premature infants with a diagnosis of ROP at Keelung CGMH between 1994 and 2003. Data on certain characteristics including gender, gestational age (GA), birth body weight (BBW), stage of ROP, and treatment modalities were collected and analyzed., Results: Among the 458 infants screened for ROP, 148 eyes of 74 premature infants were diagnosed as having ROP. Threshold ROP occurred in 24 eyes of 12 infants. The average BBW and GA were significantly lower in the threshold than in the non-threshold ROP group (p < 0.05). According to medical records of the 24 eyes of the 12 patients receiving transscleral cryotherapy, anatomical success was attained in 13 (81.3%) of 16 eyes., Conclusions: This review found low GA and BBW to be major risk factors for ROP. This review shows that transscleral cryotherapy for treating threshold ROP achieved anatomical success in about 80% of eyes. However, myopia, amblyopia, and strabismus remain major sequelae. Laser therapy is now believed to be less damaging to ocular structures and just as effective as cryotherapy in treating ROP.

Purpose: To evaluate stereopsis in term-born, preterm, and preterm children with and without retinopathy of prematurity (ROP) and its treatment. Methods: The cross-sectional study included 322 children between 3 and 11 years of age born term or preterm, with or without ROP, and with or without treatment for ROP. The ROP treatments were laser therapy, intravitreal injection (IVI) of anti-vascular endothelial growth factor, or their combination. Stereoacuity was measured using the Titmus Stereo Test, and the results among various age groups were analyzed. Results: Stereopsis was found to improve with increasing age at testing (P < 0.001) across the entire study population. The term group exhibited significantly better stereoacuity than the preterm group (P < 0.001). At 3–5 years and 6–8 years, the preterm children without ROP exhibited significantly better stereoacuity than did those with ROP (P < 0.001 and P = 0.02, respectively); however, at 9–11 years, both groups exhibited similar stereoacuity (P = 0.34). The stereoacuity in the children with untreated ROP was similar to that of the children with treated ROP in all age groups (P > 0.05). No significant differences in stereopsis were identified between children with ROP treated with laser versus with IVI (P > 0.05). From multivariate analysis, younger age at testing (P = 0.001) and younger gestational age (P < 0.001) were associated with poorer stereopsis. Conclusions: Stereopsis development gradually improved with age in all groups. The children born preterm exhibited poorer stereoacuity than those born term. Children with ROP treated with laser photocoagulation versus IVI may exhibit similar levels of stereoacuity. Younger age at testing and gestational age were independent risk factors for poorer stereoacuity. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP. [ABSTRACT FROM AUTHOR]

This study aimed to compare the clinical performance between a smartphone-based fundus photography device and a contact imaging device for retinopathy of prematurity (ROP) screening. All patients were first examined with binocular indirect ophthalmoscopy (BIO), which served as the reference standard. The patients were then assessed by two devices. Imaging quality, ability to judge the zone and stage of ROP, agreement with the BIO results, vital signs, and pain scores were compared between these two devices. In total, 142 eyes of 71 infants were included. For the smartphone-based fundus photography, image quality was graded excellent or acceptable in 91.4% of examinations, although it was still significantly inferior to that of the contact imaging device (p < 0.001). The smartphone-based fundus photography images had moderate agreement with the BIO results regarding the presence or absence of plus disease (Cohen's κ = 0.619), but evaluating the zone (p < 0.001) and stage (p < 0.001) of ROP was difficult. Systemic parameters, except for heart rate, were similar between the two imaging devices (all p > 0.05). In conclusion, although the smartphone-based fundus photography showed moderate agreement for determining the presence or absence of plus disease, it failed to identify the zone and stage of ROP. [ABSTRACT FROM AUTHOR]

Purpose:To determine the systemic impact of intravitreal injection of bevacizumab (IVB), an anti-vascular endothelium growth factor antibody, in newborn rabbits. Materials and methods:We used four groups of rabbits. Group 1 rabbits received a single injection of IVB starting from the age of 6 weeks. Group 2 rabbits received a single injection of balanced salt solution (BSS, 0.025 ml) and served as controls for group 1. Group 3 rabbits received two consecutive injections of IVB at the ages of 6 and 10 weeks. Group 4 rabbits received two consecutive injections of BSS at the ages of 6 and 10 weeks and served as controls for group 3. During the experiment, a complete blood count (CBC), clinical biochemistry, weight gain, food intake, body temperature, blood pressure, pulse, and mortality were measured in the animals. Two months after IVB injection, the animals were sacrificed, and histology of the major organs was checked. Immunohistochemistry was assessed to explore the neurons in the central nervous system (CNS). Results:We found there were no morphological or functional changes in the eyes following IVB injection. Furthermore, there were no differences in CBC, biochemistry, or other measured parameters among the four groups of animals. We checked the histology of the major organs and neurons in the CNS and they did not reveal significant differences among the four groups of animals. Conclusions:Conclusively, IVB of either one or two injections (0.625 mg) in newborn rabbit eyes is well tolerated and does not cause noticeable systemic organ pathology. [ABSTRACT FROM PUBLISHER]