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Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group ( p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group ( p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group ( p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.

Background: The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that adding postnatal weight gain to birth weight and gestational age detected 100% of cases with type 1 retinopathy of prematurity (ROP) while reducing the ROP examinations by 30%. The purpose of this study was to investigate whether being small for gestational age (SGA) affects the sensitivity and specificity of the G-ROP model., Methods: We applied the G-ROP criteria for premature infants. The infants were classified as three subgroups: SGA, appropriate for gestational age (AGA), and large for gestational age (LGA). The performance of G-ROP criteria was assessed for each group for ROP., Results: There were 41 (10.5%) SGA, 312 (80%) AGA, and 37 (9.5%) LGA neonates. Twenty-six (6.7%) neonates were treated for ROP, and the G-ROP model identified all of them. The sensitivity of the model for treatment-requiring ROP (TR-ROP) was found to be 100% in the whole patient group and for each subgroup. The specificity for TR-ROP was 46.4% for the whole group, 50% for SGA, 44% for AGA, and 63.6% for LGA. By applying the G-ROP model, the number of ROP examinations could be reduced by 25% for the whole group, 27% for SGA, 24% for AGA, and 31% for LGA, without missing TR-ROP., Conclusions: The sensitivity and specificity of the G-ROP model for TR-ROP in SGA infants were similar to the whole group. The model did not miss any cases of TR-ROP., (Copyright © 2022 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Purpose: To define late-stage fluorescein angiography (FA) findings in patients who received anti-vascular endothelial growth factor (VEGF) agents (intravitreal bevacizumab or aflibercept) as a treatment for stage 3 retinopathy of prematurity (ROP) in zone II. We also compared the findings of untreated eyes., Method: Infants with a history of ROP who underwent fluorescein angiography were evaluated retrospectively. The patients were divided into 2 groups: those who received anti-VEGF treatment and those who regressed spontaneously without treatment. Vascular abnormalities, such as vascular leakage, shunts at the vascular-avascular junction, periarteriolar areas with hypoperfusion, fine branching and blunt termination of the vessels and, were recorded., Results: Angiography evaluations revealed leakage in the eyes of 27.69% of the infants in the anti-VEGF-treated group and in 21.7% of the untreated group ( p  = .638). Among the abnormal vascular findings in the peripheral retina, the ratios of fine branching and blunt termination, numbers of shunts along the vascular-avascular junction, and sizes of periarteriolar areas of hypoperfusion were significantly larger in the untreated group than in the treated group ( p  < .05; p  < .01). The gestational ages and birth weights were significantly lower ( p  ≤ .05) in infants with vascular findings in both groups., Conclusion: Vascular abnormalities in the peripheral retina are likely due to the ROP itself. Although these abnormalities were detected by FA imaging in both treated and untreated infants with ROP, they were significantly less frequent in patients treated with anti-VEGF, indicating that anti-VEGF treatments have a partially positive effect on the retinal vascularization process.

Objective: To evaluate foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity who had laser treatment in one eye and spontaneously regressed retinopathy of prematurity in the fellow eye., Methods: Totally, 17 children (34 eyes) with a history of asymmetric course of acute Zone II retinopathy of prematurity were assessed. Data on best-corrected visual acuity, refractive status, axial length, anterior chamber depth, and optical coherence tomography angiography findings were analyzed between treated and non-treated fellow eyes., Results: Treated eyes were more myopic than non-treated eyes (mean, -0.09 ± 1.86 diopters vs mean, 0.07 ± 0.98 diopters, p  = 0.026). Compared to non-treated eyes, treated eyes had shallower anterior chamber depth (mean, 3.27 ± 0.24 mm vs mean, 3.55 ± 0.19 mm, p  = 0.02). No significant difference was observed regarding optical coherence tomography angiography parameters between two eyes of the children. The mean central foveal thickness was found to be higher in treated eyes than in non-treated eyes (297.46 ± 22.03 vs 275.55 ± 18.45, p  = 0.009). Higher number of laser spots were associated with decreased parafoveal superficial capillary plexus vessel density ( r  = -0.56, p  = 0.02) and increased central foveal thickness ( r  = 0.62, p  = 0.008)., Conclusion: Our results revealed no difference in optical coherence tomography angiography parameters between laser-treated and non-treated eyes in children with asymmetric involvement of Zone II retinopathy of prematurity except for a higher central foveal thickness in laser-treated eyes. Treated eyes were more myopic than the non-treated eyes. Number of laser applications during treatment had an impact on parafoveal superficial capillary plexus vessel density.

Purpose: To compare central foveal thickness, retinal nerve fiber layer thickness, and subfoveal choroidal thickness using swept-source optical coherence tomography in premature children with a history of treated retinopathy of prematurity (either with intravitreal bevacizumab or laser photocoagulation) or spontaneously regressed retinopathy of prematurity versus age-matched healthy children at the age of 5 years., Methods: A total of 79 children were divided into four groups: group 1, children who received intravitreal bevacizumab treatment; group 2, children who received laser photocoagulation treatment; group 3, children who had spontaneously regressed retinopathy of prematurity; and group 4, age matched, full-term healthy children. At the age of 5 years, visual functions and refractive status were assessed. The optical coherence tomography analysis was performed using swept-source optical coherence tomography (DRI-OCT Triton; Topcon, USA)., Results: There were 12 (15.2%), 23 (29.1%), 30 (38%), and 14 (17.7%) children in groups 1, 2, 3, and 4, respectively. Sex distribution was similar between the groups (p=0.420). Best corrected visual acuity was significantly better in group 4 compared with groups 1, 2, and 3 (p=0.035, p=0.001, and p=0.001, respectively). Refractive error results were similar between the groups (p=0.119). Central foveal thickness was significantly higher in group 2 than in group 1 (p=0.023). There were no significant differences observed between the groups in retinal nerve fiber layer thickness and subfoveal choroidal thickness (p>0.05)., Conclusions: Visual functional outcomes were better in term-born healthy children compared with those noted in children with a history of treated retinopathy of prematurity and spontaneously regressed retinopathy of prematurity. Laser treatment exerted a signifi-cant effect on central foveal thickness in premature children at the age of 5 years, as revealed by swept-source optical coherence tomography.

Purpose: To evaluate the efficacies and treatment outcomes following intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR), and laser photocoagulation (LPC) in retinopathy of prematurity (ROP)., Methods: This was a retrospective interventional case series study including the data of 134 infants (264 eyes) who were treated with IVB, IVR, or LPC for ROP. The data were collected from two major ROP treatment centers in Turkey without any randomization or masking. Regression of ROP, recurrence profile, complications after each treatment modality, and indications for retreatment were evaluated. The main outcome measures included the total inactivation of ROP with anatomic and refractive outcomes at 1.5 years of adjusted age., Results: There were 55 infants (41.1%) in the IVB group, 22 infants (16.4%) in the IVR group, and 57 infants (42.5%) in the LPC group. All but 3 infants (5.5%) in the IVB group and 11 infants (50%) in the IVR group showed recurrence to stage 1 and 2 ROP following IVB and IVR (p < 0.001). Retreatment was performed in three infants in both IVB and IVR groups (p = 0.098). At 1.5 years of adjusted age, all infants showed favorable anatomic outcome except one infant in the LPC group. No significant difference of the mean spherical equivalent (SE) was observed between the groups (p = 0.131). In Zone I ROP, laser treated infants had significantly higher rates of myopia and high myopia than IVB and IVR treated infants (p = 0.040 and p = 0.019, respectively)., Conclusions: Both IVB and IVR treated infants had significantly better refractive outcomes in Zone I ROP as compared to LPC treated infants at 1.5 years of adjusted age. The higher rate of disease recurrence was associated with IVR. Gestational age (GA) and the zone of ROP were also predictive factors for recurrence of ROP in the study.

Background: To assess Factor V Leiden (FVL) (rs6025), Prothrombin G20210A (rs1799963), MTHFR C677T (rs1801133), and MTHFR A1298C (rs1801131) gene mutations as risk factors in the development of retinopathy of prematurity (ROP)., Materials and Methods: A total of 105 children were included in this cross-sectional study. Patients were divided into two groups. The study group consisted of 55 infants with a history of ROP and the control group comprised 50 healthy infants with term birth. All subjects were screened for the presence of certain mutations (FVL, Prothrombin G20210A, MTHFR C677T and MTHFR A1298C) by Real-Time PCR at 1 year of age., Results: The mean gestational age (GA) and birth weight (BW) of the study group were, 28.65 ± 2.85 weeks and 1171 ± 385.74 g, respectively. There were no significant differences of genotype and allele frequency of Prothrombin G20210A, MTHFR A1298C and MTHFR C677T between the study and control groups (p > 0.05). Eight children (14.5 %) had heterozygous and one child (1.8%) had homozygous FVL mutation in the study group. One child (2%) in the control group had heterozygous FVL mutation. There was statistically significant differences of FVL allele and genotype frequencies between the groups (p < 0.05)., Conclusions: The prevalence of FVL polymorphism (16.3 %) was higher in ROP patients than control subjects in this Turkish cohort. We suggest a possible association of FVL mutation with ROP at the end of the study.

Purpose: To demonstrate the clinical characteristics and treatment outcomes of severe retinopathy of prematurity (ROP) in preterm infants with birth weight (BW) above 1500 g in Turkey., Methods: A retrospective review of 5920 ROP records was performed in Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital. The records were obtained from ROP treatment center of the same institute between 2011 and 2016. The data comprised the demographic and clinical characteristics including, gestational age, BW, systemic risk factors, zone and stage of ROP, ROP type, treatment modality, treatment outcomes and inborn/outborn status of the babies., Results: A total of 36 infants (71 eyes) with severe ROP and BW> 1500 g were retrieved. There were 30 infants (83.3%) with type 1 ROP and 6 infants (16.7%) with aggressive posterior ROP (APROP). 3 infants (8.3%) were born at our hospital whereas 33 (91.7%) were referred from outer private neonatal intensive care unit (NICU) centers. Zone I APROP was detected during the initial screening. 21 infants (58.3%) underwent laser treatment while 15 (41.7%) received intravitreal bevacizumab (IVB) injections. No unfavorable structural outcome was observed following either treatment modality., Conclusion: Severe ROP may occur in heavier preterm infants. Laser treatment and IVB injections were useful in selected cases. Presence of APROP at first examination suggests an earlier screening in heavier babies. Standardization of private NICU centers as well as establishing a national ROP protocol is necessary in Turkey., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To assess ocular biometric outcomes following intravitreal bevacizumab (IVB) monotherapy for retinopathy of prematurity (ROP) and compare these results with those of laser photocoagulated infants and with the ones with spontaneously regressed ROP., Materials and Methods: Premature infants including those who underwent IVB monotherapy (Group 1) or laser photocoagulation (Group 2) for ROP and infants with spontaneously regressed ROP (Group 3) were recruited for the study. Refractive errors and ocular biometric parameters (Axial length [AL], anterior chamber depth [ACD], and lens thickness [LT]) were measured at adjusted 1 year of age in all subjects., Results: There was no significant difference of spherical equivalent (SE) value between the groups (P = 0.781). The incidence of high myopia was 7.4% in Group 1 and 12.7% in Group 2 (P = 0.081). No infants exhibited high myopia in Group 3. LT was greater in Group 2 when compared to Group 1 and Group 3 (P = 0.011). Lower SE was significantly correlated to longer AL in Group 1 (r = -0.656, P = 0.015). There was a significant positive correlation between SE and ACD values in Group 2 (r = 0.391, P = 0.005)., Conclusion: The study showed no significant difference of SE between the groups. High myopia was only present among the treated infants either with IVB or laser. Infants who received laser treatment significantly had thicker lenses.

Purpose: To evaluate the effect of a single intravitreal bevacizumab (IVB) injection on blood flow parameters in the ophthalmic artery (OA) and middle cerebral artery (MCA) in infants with retinopathy of prematurity (ROP)., Materials and Methods: This prospective and interventional study included 15 infants with ROP who were treated with IVB. Peak systolic velocity (PSV), end-diastolic velocity, mean velocity (MV) and resistivity index were measured using pulse wave Doppler ultrasonography (Philips En Visor C, Amsterdam, The Netherlands) in the OA and MCA, before IVB injection and 1 day, 1 week and 1 month after IVB injection., Results: Measurements of PSV-OA, MV-OA and PSV-MCA showed significant changes after IVB treatment (p = 0.01, p = 0.02, p = 0.02, respectively). The PSV-OA measurements at 1 week and 1 month were significantly lower than the baseline PSV-OA measurement (p = 0.03 and p = 0.01, respectively). The MV-OA measurement was significantly lower at 1 month following IVB as compared to the baseline MV-OA measurement (p = 0.03). The PSV-MCA showed a significant decline 1 day after IVB injection (p = 0.03)., Conclusions: The study demonstrated that IVB causes significant alterations in blood flow parameters in the OA and MCA predicted by Doppler ultrasonography in infants with ROP., (© 2016 S. Karger AG, Basel.)

Purpose: To evaluate 2-year outcomes following intravitreal bevacizumab (IVB) as monotherapy for aggressive posterior retinopathy of prematurity (APROP)., Methods: Medical records of 40 infants were retrospectively reviewed. Group I included infants who had received IVB injections for APROP. Group II included infants who underwent laser treatment for APROP. Anatomic and refractive outcomes and the presence of anisometropia and strabismus were assessed at follow-up examinations., Results: Group I included 48 eyes of 25 infants (11 males) with a mean gestational age (GA) of 26.40 ± 1.82 weeks and a mean birth weight (BW) of 901.40 ± 304.60 g. Group II included 30 eyes of 15 infants (6 males) with a mean GA of 27.30 ± 1.82 weeks and a mean BW of 941.00 ± 282.48 g. GA, BW, and gender distributions were similar between groups (P=0.187, P=0.685, and P=1.000, respectively). Refractive errors were significantly less myopic in group I (0.42 ± 3.42 D) than in group II (-6.66 ± 4.96 D) at 2 years (P=0.001). Significantly higher rates of anisometropia and strabismus were observed in group II than in group I (P=0.009 and P=0.036, respectively)., Conclusions: The study demonstrated that IVB monotherapy can be useful in the treatment of APROP. The decreased incidence of early unfavorable refractive and functional outcomes in the IVB group compared with the laser group showed a potential benefit for patients treated with IVB, and this needs to be better evaluated in future prospective studies.

Purpose: To describe the clinical and demographical characteristics and treatment outcomes of the premature infants who were presented with the signs of anterior segment ischemia (ASI) following transpupillary diode laser photocoagulation for aggressive posterior retinopathy of prematurity (APROP)., Methods: The records of the premature infants who developed ASI following bilateral laser photocoagulation between November 2010 and December 2013 in a single institution for the treatment of APROP were retrospectively reviewed. The clinical and demographical characteristics, laser parameters, anterior segment complications, and structural outcomes were evaluated., Results: Nine eyes of five infants (three males, two females) were recruited for the study. Mean gestational age (GA), birth weight (BW), and postmenstrual age (PMA) at the time of laser ablation were 28.2 ± 2.5 weeks, 1,287.0 ± 483.4 g and 34.8 ± 2.2 weeks, respectively. All eyes were treated with a near-confluent pattern of laser ablation. Several anterior segment complications were observed including corneal edema (nine eyes), posterior synechia (nine eyes), pupillary membranes (five eyes), shallow anterior chamber (three eyes), hyphema (three eyes), and focal lens opacities (two eyes), of all resolved completely. Permanent dense cataracts observed in two eyes of two infants who were scheduled for lensectomy and anterior vitrectomy. None of the eyes progressed to phthisis bulbi., Conclusions: Anterior segment ischemia after laser treatment of APROP is a rarely encountered clinical entity. Mild and transient cases may resolve without any long-term sequelae but severe ones may progress to permanent cataract requiring further surgery.

The purpose of the study is to evaluate the clinical outcome of laser photocoagulation (LPC) in the treatment of retinopathy of prematurity (ROP) at a referral hospital in Turkey. In this retrospective study, a chart review of infants who underwent LPC for ROP between June 2011 and June 2013 was done. Clinical and demographic characteristics, laser parameters, anatomic, and refractive outcomes were evaluated. Totally 113 infants (202 eyes) were enrolled in the study. Of the 202 eyes, 29 eyes had threshold ROP, 141 eyes had prethreshold ROP, and 32 eyes had aggressive posterior ROP (APROP) at initial interventions. The mean gestational age (GA) was 28.13 ± 1.99 weeks (range between 24 and 33 weeks), the mean birth weight (BW) was 1,147.77 ± 341.77 g (range between 530 and 2,000 g) and the mean postmenstrual age (PMA) at first laser treatment time was 35.79 ± 1.74 weeks (range between 33 and 39 weeks). The mean number of laser spots (NLS) applied for each eye was 1,358.05 ± 369.91. Eyes with APROP had higher number of NLS than eyes with threshold ROP and prethreshold ROP (P < 0.01). Anatomic outcome was favorable for 171 eyes (84.7 %) at the end of the 1-year follow-up. Refractive data were available for 56 infants (100 eyes). The mean refractive error was 0.00 ± 2.48D SE. The incidence of high myopia (>5D) and strabismus was 2 and 14.3 %, respectively. Laser photocoagulation is an effective therapy for ROP. Early and appropriate laser treatment improves the clinical outcome of the disease.

Purpose: To report the baseline plasma levels of vascular endothelial growth factor-A (VEGF-A), soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) and soluble Tie2 in infants with treatment-requiring retinopathy of prematurity (ROP) and to investigate the effect of laser treatment on the plasma levels., Methods: Blood samples were collected from infants with prethreshold type 1 ROP before, 1 day after, and 1 week after confluent laser photocoagulation. Enzyme-linked immunosorbent assay procedure was used to determine plasma VEGF-A, sVEGFR-2, and sTie2 levels., Results: A total of 48 eyes of 30 infants were included. The mean postconceptional age at which laser photocoagulation was performed was 37.5 ± 2.9 weeks. The mean number of laser spots applied to each eye was 1,480 ± 420. Regression of active retinopathy occurred within 1 week of treatment in all cases. Baseline plasma VEGF-A, sVEGFR-2, and sTie2 levels did not differ between unilateral and bilateral and also zone I and zone II disease. A significantly progressive decrease was observed in plasma VEGF-A, sVEGFR-2, and sTie2 levels at 1 day and 1 week after laser photocoagulation., Conclusions: Plasma levels of VEGF-A, sVEGFR-2, and sTie2 decreased significantly in our patients after laser treatment; however, because of the variability in the measurements, further studies evaluating the clinical value of these angiogenic factors in patients with treatment-requiring ROP are necessary., (Copyright © 2014 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)