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

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

Intravitreal bevacizumab to treat retinopathy of prematurity in 865 eyes: a study to determine predictors of primary treatment failure and recurrence.

PURPOSE: This study aimed to evaluate the rate and risk factors for primary failure and recurrence after intravitreal anti-VEGF injection in retinopathy of prematurity (ROP). METHODS: This retrospective study was performed on 865 eyes from 441 patients with retinopathy of prematurity receiving intravitreal bevacizumab from 2012 to 2019. Medical records of patients were evaluated. RESULTS: Mean gestational age (GA) and birth weight of patients were 28 ± 2 weeks and 1121 ± 312 g, respectively. Thirty-five eyes (4.04%) had a primary failure, including 18 eyes from 187 eyes in zone 1 (9.6%) and 17 eyes from 678 eyes in zone 2 (2.5%). The mean time of retreatment was 16.64 ± 13.68 days in eyes without regression ROP. The remaining 830 eyes (95.95%) were included in recurrence analysis. The recurrence occurred in 33 eyes (3.97%) of them in 20 patients, with the meantime of 77.52 days after the first treatment (IVB). The presence of plus disease, history of oxygen therapy or phototherapy, and GA less than 32 were associated with significantly increased prevalence of treatment failure. The risk factors predicting recurrence are lower birth weight, zone 1 pretreatment, history of intubation, anemia, and sepsis. CONCLUSION: Intravitreal anti-VEGF is a successful treatment for ROP with a low rate of primary failure and recurrence. Awareness of risk factors for treatment failure and recurrence may help clinicians to schedule more vigilant approach in susceptible cases.

Prevalence and risk factors of retinopathy of prematurity in Iran: a systematic review and meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) refers to the developmental disorder of the retina in premature infants and is one of the most serious and most dangerous complications in premature infants. The prevalence of ROP in Iran is different in various parts of Iran and its prevalence is reported to be 1-70% in different regions. This study aims to determine the prevalence and risk factors of ROP in Iran. METHODS: This review article was conducted based on the preferred reporting items for systematic review and meta-analysis (PRISMA) protocols. To find literature about ROP in Iran, a comprehensive search was done using MeSH keywords in several online databases such as PubMed, Ovid, Science Direct, EMBASE, Web of Science, CINAHL, EBSCO, Magiran, Iranmedex, SID, Medlib, IranDoc, as well as the Google Scholar search engine until May 2017. Comprehensive Meta-analysis Software (CMA) Version 2 was used for data analysis. RESULTS: According to 42 studies including 18,000 premature infants, the prevalence of ROP was reported to be 23.5% (95% CI: 20.4-26.8) in Iran. The prevalence of ROP stages 1, 2, 3, 4 and 5 was 7.9% (95% CI: 5.3-11.5), 9.7% (95% CI: 6.1-15.3), 2.8% (95% CI: 1.6-4.9), 2.9% (95% CI: 1.9-4.5) and 3.6% (95% CI: 2.4-5.2), respectively. The prevalence of ROP in Iranian girls and boys premature infants was 18.3% (95% CI: 12.8-25.4) and 18.9% (95% CI: 11.9-28.5), respectively. The lowest prevalence of ROP was in the West of Iran (12.3% [95% CI: 7.6-19.1]), while the highest prevalence was associated with the Center of Iran (24.9% [95% CI: 21.8-28.4]). The prevalence of ROP is increasing according to the year of study, and this relationship is not significant (p = 0.181). The significant risk factors for ROP were small gestational age (p < 0.001), low birth weight (p < 0.001), septicemia (p = 0.021), respiratory distress syndrome (p = 0.036), intraventricular hemorrhage (p = 0.005), continuous positive pressure ventilation (p = 0.023), saturation above 50% (p = 0.023), apnea (p = 0.002), frequency and duration of blood transfusion, oxygen therapy and phototherapy (p < 0.05), whereas pre-eclampsia decreased the prevalence of ROP (p = 0.014). CONCLUSION: Considering the high prevalence of ROP in Iran, screening and close supervision by experienced ophthalmologists to diagnose and treat the common complications of pre-maturity and prevent visual impairment or blindness is necessary.

Automated diagnosis of plus disease in retinopathy of prematurity using quantification of vessels characteristics.

The condition known as Plus disease is distinguished by atypical alterations in the retinal vasculature of neonates born prematurely. It has been demonstrated that the diagnosis of Plus disease is subjective and qualitative in nature. The utilization of quantitative methods and computer-based image analysis to enhance the objectivity of Plus disease diagnosis has been extensively established in the literature. This study presents the development of a computer-based image analysis method aimed at automatically distinguishing Plus images from non-Plus images. The proposed methodology conducts a quantitative analysis of the vascular characteristics linked to Plus disease, thereby aiding physicians in making informed judgments. A collection of 76 posterior retinal images from a diverse group of infants who underwent screening for Retinopathy of Prematurity (ROP) was obtained. A reference standard diagnosis was established as the majority of the labeling performed by three experts in ROP during two separate sessions. The process of segmenting retinal vessels was carried out using a semi-automatic methodology. Computer algorithms were developed to compute the tortuosity, dilation, and density of vessels in various retinal regions as potential discriminative characteristics. A classifier was provided with a set of selected features in order to distinguish between Plus images and non-Plus images. This study included 76 infants (49 [64.5%] boys) with mean birth weight of 1305 ± 427 g and mean gestational age of 29.3 ± 3 weeks. The average level of agreement among experts for the diagnosis of plus disease was found to be 79% with a standard deviation of 5.3%. In terms of intra-expert agreement, the average was 85% with a standard deviation of 3%. Furthermore, the average tortuosity of the five most tortuous vessels was significantly higher in Plus images compared to non-Plus images (p ≤ 0.0001). The curvature values based on points were found to be significantly higher in Plus images compared to non-Plus images (p ≤ 0.0001). The maximum diameter of vessels within a region extending 5-disc diameters away from the border of the optic disc (referred to as 5DD) exhibited a statistically significant increase in Plus images compared to non-Plus images (p ≤ 0.0001). The density of vessels in Plus images was found to be significantly higher compared to non-Plus images (p ≤ 0.0001). The classifier's accuracy in distinguishing between Plus and non-Plus images, as determined through tenfold cross-validation, was found to be 0.86 ± 0.01. This accuracy was observed to be higher than the diagnostic accuracy of one out of three experts when compared to the reference standard. The implemented algorithm in the current study demonstrated a commendable level of accuracy in detecting Plus disease in cases of retinopathy of prematurity, exhibiting comparable performance to that of expert diagnoses. By engaging in an objective analysis of the characteristics of vessels, there exists the possibility of conducting a quantitative assessment of the disease progression's features. The utilization of this automated system has the potential to enhance physicians' ability to diagnose Plus disease, thereby offering valuable contributions to the management of ROP through the integration of traditional ophthalmoscopy and image-based telemedicine methodologies.

Comparison of aflibercept and bevacizumab in the treatment of type 1 retinopathy of prematurity.

BACKGROUND: To evaluate the outcome of intravitreal bevacizumab (IVB) and aflibercept (IVA) injection for patients with retinopathy of prematurity (ROP). METHODS: In this single-center retrospective cohort, the recorded medical data of the infants who had been undergone intravitreal injection with either bevacizumab or aflibercept for type 1 ROP were reviewed. The infants were allocated into two groups. IVB group included patients who were treated with bevacizumab as initial treatment and the IVA group included patients who were treated with aflibercept as initial treatment. The rate and time of complete regression, as well as the recurrence rates, were compared between the groups. RESULTS: A total of 889 eyes of 453 infants were enrolled in the study. There were 865 eyes of 441 infants in the IVB group and 24 eyes of 12 infants in the IVA group. Follow-up time was 289 ± 257 days in the IVB group and 143 ± 25 days in the IVA group (p < 0.001). The difference in the ROP zone was not statistically significant between the 2 treatment groups (p = 0.328). All eyes in the IVA group showed initial regression of ROP after the intravitreal injections. These regressions were achieved in 830 (96.0%) eyes that were injected with IVB (p = 0.023). The median observed regression time was 10 days and 16 days in eyes treated with bevacizumab and aflibercept respectively. Recurrence was noted in 3.9% of eyes (34/865) in the IVB group and 58.3% of eyes (14/24) in the IVA group (p < 0.001). CONCLUSION: While the regression rate in the IVA group was significantly higher than in the IVB group, the recurrence rate was significantly more in the IVA group, which may be attributed to differences in the pharmacokinetics of these drugs in the vitreous body.

Ocular complications following intravitreal bevacizumab injection for retinopathy of prematurity and assessment of risk factors.

PURPOSE: Laser ablation of the avascular peripheral retina has been the standard method of ROP treatment. Intravitreal anti-VEGF is useful in the management of ROP patients, especially for aggressive posterior ROP. However, ocular and systemic complication after intravitreal bevacizumab was the main concern. This study aimed to investigate the treatment-related ocular and systemic complications of intravitreal bevacizumab (IVB) in patients with retinopathy of prematurity (ROP). METHOD: This retrospective study included neonates receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) to treat ROP. Medical records of the patients were evaluated about the ocular complications after receiving IVB from 2012 to 2019. Treatment-related complications (vitreous hemorrhage, glaucoma, cataract, hyphema, corneal abrasion/opacity, and endophthalmitis), and disease-progression signs including retinal fold or stage 4 or 5 detachment were documented. Any reports of systemic events after injections were also recorded. RESULT: Mean gestational age and birth weight of 441 patients receiving IVB for type-1 ROP were 28 ± 2 (22-34 weeks) and 1121 ± 312 (550-2700 g), respectively. The median follow-up after treatment in all patients and patients with complications was 289.43 ± 257 days (5-1899 days) and 385.89 ± 311.59 (196-1192) days, respectively. Out of 865 eyes, 20 eyes (2.31%, 95% Clopper-Pearson Confidence Interval: 1.14-3.54%) have been affected by ocular complications. The rates of different complications included progression of retinopathy in 17 eyes (1.96%), cataracts in 2 eyes (0.23%), and vitreous hemorrhage in one eye (0.11%). No cases of endophthalmitis, thromboembolic events, or death occurred in this study. We evaluated the prevalence ratio (PR) on the multiple risk factors to determine the prediction of the complications. The existence of neovascularization of iris has the highest susceptibility to predict the complication (PR = 5.091, P-value 0.014) following by the presence of retinopathy in zone 1 of the infant's retina (PR = 4.386, P-value = 0.010). CONCLUSION: The incidence rate of complications related to Intravitreal bevacizumab injection was low, which was compatible with previous studies. Bevacizumab injection seems well tolerated in most cases of ROP. Iris neovascularization and the presence of retinopathy in zone 1 were associated with a higher occurrence of complications than the absence of these risk factors.