Foveal structure changes in infants treated with anti-VEGF therapy or laser therapy guided by optical coherence tomography angiography for retinopathy of prematurity

AIM: To evaluate foveal vessel density (VD) and foveal thickness using optical coherence tomography angiography (OCTA) in retinopathy of prematurity (ROP) children treated with laser photocoagulation or anti-vascular endothelial growth factor (VEGF) injection. Additionally, we assessed the relationship between foveal microvascular anomalies and different therapies in ROP children. METHODS: This was a single-center, retrospective study of patients with a diagnosis of type 1 ROP. Twenty-three eyes (14 patients) treated with anti-VEGF injection and twenty-nine eyes (17 patients) treated with laser coagulation were included in this study. The foveal VD, inner thickness and full thickness were measured at the central 0°, 2° to 8°, and 8° of the retina (centered on the fovea) using OCTA and cross-sectional OCT, respectively. RESULTS: Foveal VD, inner thickness and full thickness were significantly smaller within the central 8° of the retina in ROP children treated with anti-VEGF injection than in those treated with laser photocoagulation (P=0.013, 0.009, 0.036, respectively). The full thickness was also smaller in the anti-VEGF group than in the laser group at the central 0° of the retina (P=0.010). The grade of foveal hypoplasia is lower in the anti-VEGF group than in the laser group (P=0.045). Multivariable analysis did not find any risk factors associated with visual acuity in our study. CONCLUSION: In children with type 1 ROP, the better structural development of fovea in those who were treated with anti-VEGF injection compared with laser photocoagulation are identified. However, visual acuity outcomes are similar 70mo after the treatments.

Retrospective validation of the postnatal Growth and Retinopathy of Prematurity (G-ROP) criteria in a Swiss cohort

Background Currently used screening criteria for retinopathy of prematurity (ROP) show high sensitivity for predicting treatment-requiring ROP but low specificity; over 90% of examined infants do not develop ROP that requires treatment (type 1 ROP). A novel weight gain-based prediction model was developed by the G-ROP study group to increase the specificity of the screening criteria and keep the number of ophthalmic examinations as low as possible. This retrospective cohort study aimed to externally validate the G-ROP screening criteria in a Swiss cohort. Methods Data from 645 preterm infants in ROP screening at Inselspital Bern between January 2015 and December 2019 were retrospectively retrieved from the screening log and analysed. The G-ROP screening criteria, consisting of 6 trigger parameters, were applied in infants with complete data. To determine the performance of the G-ROP prediction model for treatment-requiring ROP, sensitivity and specificity were calculated. Results Complete data were available for 322 infants who were included in the analysis. None of the excluded infants had developed type 1 ROP. By applying the 6 criteria in the G-ROP model, 214 infants were flagged to undergo screening: among these, 14 developed type 1 ROP, 9 developed type 2 ROP, and 43 developed milder stages of ROP. The sensitivity for predicting treatment-requiring ROP was 100% (CI, 0.79–1.00), and the specificity was 41% (CI, 0.35 –0.47). Implementing the novel G-ROP screening criteria would reduce the number of infants entering ROP screening by approximately one third. Conclusions The overall prevalence of treatment-requiring ROP was low (2.15%). Previously published performance parameters for the G-ROP algorithm were reproducible in this Swiss cohort. Importantly, all treatment-requiring infants were correctly identified. By using these novel criteria, the burden of screening examinations could be significantly reduced.

Time to regain birth weight - a marker to predict the severity of retinopathy of prematurity?

Background Poor weight gain in the first few weeks of life has been studied as a predictor of retinopathy of prematurity (ROP). Our aim was to assess whether time taken to regain birthweight (BW) be used as an additional marker to identify infants with type 1 ROP. Methods In this retrospective study, preterm infants (< 27 weeks gestational age at birth) born during the period from 1/1/2010–31/12/2015 at a tertiary neonatal intensive care unit in Australia were included. Twenty-seven preterm infants with Type 1 ROP were identified. Controls (No ROP or ROP other than type 1) were matched with cases on gestational age at birth and BW (1:4 ratio). Data were collected from the database and medical records. Results The median (IQR) gestational age for Type 1 ROP and control groups were 24 (24–26) and 25 (24–26) weeks respectively and median (IQR) BW for Type 1 ROP and control groups were 675 (635–810) and 773 (666–884) grams respectively. Preterm infants with Type 1 ROP were more likely to be small for gestational age (SGA) (18.5% vs 3.7%, p = 0.015) and had increased weeks on oxygen therapy (median 11.9 vs 9.1, p = 0.028). Time to regain BW was longer in preterm infants with type 1 ROP than controls but did not reach statistical significance (median 9 vs 7 days, OR 1.08, 95% CI 1.00–1.17, p = 0.059) adjusted for SGA and duration of oxygen therapy. The area under the curve from the time to regain BW model with adjustment for SGA and duration of oxygen therapy was 0.73 (95% CI 0.62–0.83). Conclusion We hypothesize that time to regain BW has potential to aid prediction of Type 1 ROP and this warrants further investigation in a larger prospective study.

Thrombocytopenia as Type 1 ROP Biomarker: A Longitudinal Study

This study aimed to prospectively evaluate the association between the appearance and evolution of retinopathy of prematurity (ROP) and selected blood parameters, focusing on platelets count. In total, 157 preterm consecutive babies screened for ROP were included and classified in: ROP necessitating treatment (group ROP1), ROP regressed without therapy (group ROP2) and no ROP (group no-ROP), divided in two phases for each group depending on gestational age. Blood parameters were weekly gathered and referred to postmenstrual age, ROP severity and phase. Platelet count mean values were statistically lower (p < 0.001) during both phases in ROP1 group (179 × 109/L vs. 213 × 109/L in phase 1 and 2, respectively) vs. other groups (ROP2: 286 × 109/L vs. 293 × 109/L; no ROP: 295 × 109/L vs. 313 × 109/L). Platelet count at birth <181 × 109 was statistically associated with Type 1 ROP development and evolution (sensibility = 76.47%, 95% confidence interval 60.0–87.6; specificity = 66.12%, 95% confidence interval 57.3–73.9). In ROP 1 group, a platelets count mean value “spike” (392.6 × 109/L) was documented at 36 weeks of corrected gestational age, preceding the need for treatment performed at a median of 38.1 ± 3.2 weeks. Early birth thrombocytopenia is confirmed as a biomarker of development and progression of ROP requiring treatment. The increase of platelets count at 35–37 weeks of corrected gestational age can be considered a possible clinical biomarker anticipating Type 1 ROP progression in preterm infants.

Severe Retinopathy of Prematurity Is Not Independently Associated With Worse Neurodevelopmental Outcomes in Preterm Neonates

Purpose: To evaluate the relationship between retinopathy of prematurity (ROP) severity and neurodevelopmental outcomes in premature neonates at 0–36 months corrected age.Methods: A retrospective chart review was performed on 228 neonates screened for ROP at the UCLA Mattel Children's Hospital between 2011 and 2018. Demographic information, clinical outcomes, ROP severity (no ROP, type 1 ROP, type 2 ROP), and Bayley-III neurodevelopmental scores were collected. Infants were grouped into corrected age cohorts (0–12, 12–24, and 24–36 months) to assess neurodevelopmental outcomes with increasing age. Within each age cohort, ANOVA and Chi-Square testing were used to detect differences in birth characteristics and neurodevelopmental scores between infants with type 1 ROP, type 2 ROP, or no ROP. Univariable analyses assessed the relationship between ROP severity and neurodevelopmental outcomes within each age cohort. A multivariable analysis was then performed to determine if ROP severity remained significantly associated with worse neurodevelopmental scores after controlling for birth weight (BW), intraventricular hemorrhage grade (IVH), health insurance type, male sex, and age at Bayley testing.Results: Without controlling for factors associated with prematurity, neonates with type 1 ROP had poorer cognition (p = 0.001) and motor (p = 0.006) scores at ages 0–12 months and poorer cognition (p = 0.01), language (p = 0.04) and motor (p = 0.04) scores at ages 12–24 months than infants without ROP, but no significant differences were detected at ages 24–36 months. After adjusting for BW, IVH, insurance type, male sex, and age at Bayley testing, ROP severity was no longer associated with worse neurodevelopmental scores in any domain.Conclusion: This study emphasizes that poorer neurodevelopmental outcomes in preterm neonates are most likely related to lower birthweight, associated co-morbidities of prematurity, and socioeconomic factors such as health insurance, not severity of ROP itself.

Validation of the postnatal growth and retinopathy of prematurity screening criteria: A retrospective Italian analysis

Purpose: Retinopathy of prematurity (ROP) is the leading cause of childhood blindness. The aim of our study is to validate the new screening criteria elaborated by the Postnatal Growth and Retinopathy of Prematurity (G-ROP) study group in a monocentric cohort of Italian preterm infants. Methods: We retrospectively applied the G-ROP screening criteria to a cohort of preterm infants born between May 2015 and July 2020 with known birth weight, gestational age, serial weight measurement, and known ROP outcome. Primary outcomes were sensitivity and specificity of ROP detection, especially of treatment requiring ROP. Secondary outcomes were reduction of ophthalmologic examinations and of infants requiring screening. Results: We retrospectively evaluated 595 children and 475 were included in our study. Of them, 119 developed any type ROP, 39 developed type 1 ROP, and 28 underwent treatment. G-ROP criteria predicted 39 of 39 cases of type 1 ROP (100% sensitivity and specificity). Sensitivity and specificity for detection of treated ROP were 100%. Considering any type ROP detection, sensitivity was 87.4% and specificity was 100%. Our analysis showed that screening could be avoided in 50% of patients, resulting in a 29% reduction of the number of examinations. Conclusions: Our study validates the new G-ROP screening protocol in a monocentric cohort of premature infants. We demonstrate that all Type 1 ROP and requiring treatment ROP could be found even with a reduction of eye examinations.

Systemic conbercept pharmacokinetics and VEGF pharmacodynamics following intravitreal injections of conbercept in patients with retinopathy of prematurity

BackgroundData on serum vascular endothelial growth factor (VEGF) and drug levels in patients with retinopathy of prematurity (ROP) following intravitreal injections of conbercept (IVC) are lacking.MethodsMulticentre, prospective, non-randomised study of patients with aggressive posterior retinopathy of prematurity (APROP) or type 1 ROP who had not received other treatment. All infants received therapy in both eyes plus intravitreal IVC 0.25 mg/0.025 mL in one eye and had at least 6 months of follow-up. Blood samples were collected before and 1 week and 4 weeks after IVC. The main outcome measures were serum conbercept and VEGF concentrations.ResultsForty infants with APROP or type 1 ROP were enrolled. The mean serum VEGF at baseline and 1 week and 4 weeks after a total of 0.25 mg of IVC was 953.35±311.90 pg/mL, 303.46±181.89 pg/mL and 883.12±303.89 pg/mL, respectively. Serum VEGF 1 week after IVC was significantly lower (p<0.05) than baseline, and at 4 weeks after IVC, it was significantly higher (p<0.05) than at 1 week. There was no significant difference (p>0.05) between baseline and 4 weeks. Serum conbercept was below the limit of quantitation (BLOQ) at baseline and 4 weeks and was 19.81±7.60 ng/mL at 1 week.ConclusionSerum VEGF 1 week after IVC was significantly lower than baseline but returned to baseline at 4 weeks. Serum conbercept increased at 1 week and was BLOQ at 4 weeks.

Validity and reliability of ROPScore scoring method to predict the severity of retinopathy of prematurity in premature infants

Purpose: To assess the accuracy and efficacy of ROPScore scoring system an ancillary method to predict the severity of retinopathy of prematurity (ROP) in very low birth weight (VLBW) premature infants. Methods: The medical records of 131 premature babies having a birth weight  1500 gram and gestational age (GA) ≤ 30 weeks were included in this study. The ROPScore was calculated for each baby at six weeks of life using an Excel spreadsheet (Microsoft®). Area under curve (AUC) analysis was used in both any stage of ROP and type-1 (severe) ROP to ascertain the cut-off points for the scoring model. Sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of the scoring system with the calibrated cut-off points were analyzed. Results: The sensitivity of the ROPScore scoring system was 88.5% ( 95% CI 79-94) and 100% (95% CI 82-100) was for predicting any stage and type-1 retinopathy of prematurity, respectively. The PPV and NPV of the models were 62% and 74.1% for any stage of ROP and those of were 50% and 100% for type-1 ROP, respectively. In ROC analysis, the mean AUCs of ROPScore model was statistically significant compared than BW and GA for predicting type -1 ROP (p < 0.001). Conclusion: This study indicated that ROPScore scoring model with customized cutoff levels might be a useful method for early prediction of premature retinopathy, particularly in type-1 (severe) ROP. In addition, this model may also reduce the number of eye examinations which are essential for detecting the retinopathy of prematurity

80 Years of vision: preventing blindness from retinopathy of prematurity

Retinopathy of prematurity (ROP) is one of the leading yet preventable causes of childhood blindness worldwide. The purpose of this review is to provide a practical template for observational and treatment methods in order to reduce the overall incidence of any ROP and to improve both short-term and long-term outcomes once Type 1 ROP (treatable ROP) develops.