Ranibizumab For Retinopathy Of Prematurity Research Articles

Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity.

To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. In this retrospective study, the premature children aged 4 to 9years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

Refractive status and retinal morphology in children with a history of intravitreal ranibizumab for retinopathy of prematurity.

This study investigated the characteristics of refractive status, visual acuity, and retinal morphology in children with a history of receiving intravitreal ranibizumab for retinopathy of prematurity (ROP). Children 4-6years of age were enrolled and divided into the following four groups: group 1, children with a history of ROP who had been treated with intravitreal ranibizumab; group 2, children with a history of ROP who had not received any treatment; group 3, premature children without ROP; and group 4, full-term children. Refractive status, peripapillary retinal nerve fiber layer (RNFL), and macular thickness were measured. A total of 204 children were enrolled. In group 1, myopic shift was not noted, but poorer best corrected visual acuity (BCVA) and shorter axial length were observed. Significantly lower peripapillary RNFL thickness in the average total and superior quadrant, higher central subfield thickness, lower parafoveal retinal thickness in average total, superior, and nasal and temporal quadrants were observed in group 1 than in the other groups. The poor BCVA in patients with ROP was correlated with the lower RNFL thickness in the superior quadrant. Conclusion: Children with a history of type 1 ROP treated with ranibizumab did not show a myopic shift but did show abnormal retinal morphology and the poorest BCVA among all groups. We suggest that pediatric ophthalmologists should always pay attention to visual development in patients with ROP with a history of intravitreal ranibizumab. What is Known: • Anti-VEGF is efficiently and widely used in the treatment of type 1 retinopathy of prematurity (ROP), and different anti-VEGF agents are associated with different prevalence of myopia. • Patients with ROP who receive treatment such as laser therapy or cryotherapy have abnormal macular development and retinal nerve fiber layer (RNFL) thickness. What is New: • Children with a history of ROP treated with intravitreal ranibizumab did not show a myopic shift but did show poor BCVA at 4-6years of age. • Abnormal macular morphology and lower peripapillary RNFL thickness were found in these children.

Appropriate dose of intravitreal ranibizumab for ROP: a retrospective study

ObjectiveTo compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab.SubjectsAll patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study.MethodsEighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed.ResultsGA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient.ConclusionTreatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.

Refractive error outcomes after intravitreal ranibizumab for retinopathy of prematurity

BackgroundTo evaluate the refractive outcomes in children treated with intravitreal injection of ranibizumab (IVR) for retinopathy of prematurity (ROP).MethodsA retrospective study of 95 patients (186 eyes) was conducted. All patients received IVR treatment. The cycloplegic refraction was evaluated at three months, six months, 12-months and 24-months.ResultThe average spherical equivalent (SE) refraction value for patients with ROP who were treated with IVR as a monotherapy at the three, six, 12 and 24-months was +1.84 ± 2.11-D, +1.02 ± 2.41-D, +0.43 ± 2.23-D and +0.13 ± 2.73-D, respectively (p < 0.001). Myopia (SE < −0.25-D) was observed in 24 eyes (15.9 per cent) at the three‐month follow‐up, 33 eyes (21.8 per cent) at the six‐month follow‐up, 33 eyes (26.5 per cent) at the 12‐month follow‐up and 34 eyes (37.5 per cent) at the 24‐month follow‐up, respectively (p < 0.05). The percentage of eyes with high myopia (SE < −5.0 D) was 0.6 per cent, 1.4 per cent, 1.7 per cent and 3.4 per cent at the three‐month, six‐month, 12‐month and 24‐month follow‐up visits in the IVR group. There were 59 eyes that received repeated IVR injections at the follow‐ups. The average SE of patients receiving repeated injections at the three‐, six‐, 12‐ and 24‐month visits was +1.53 ± 2.03-D, +1.25 ± 1.95-D, +0.58 ± 2.24-D and −0.17 ± 3.22-D, respectively (p = 0.04).ConclusionOur large sample study found that 37.5 per cent and 3.4 per cent of patients treated with IVR developed myopia and high myopia respectively, at the 24‐month follow‐up. Furthermore, the mean SE decreased, and the trend of myopia increased, in the IVR group at the follow‐ups. Repeated injections might promote myopia in ROP patients. The refractive status needs to be monitored in patients treated with ranibizumab.

Fluorescein Angiographic Findings of Peripheral Retinal Vasculature after Intravitreal Conbercept versus Ranibizumab for Retinopathy of Prematurity.

Purpose To evaluate angiographic findings of peripheral retina vasculature in retinopathy of prematurity (ROP) neonates who received intravitreal conbercept (IVC) or ranibizumab (IVR). Methods Fluorescein angiography (FA) findings were retrospectively evaluated for ROP neonates who received IVC or IVR. Outcome measures included peripheral avascular zone, vascular leakage, vascular blunting, vascular loops, vascular dilatation, arteriovenous shunt, and capillary dropout. Results Fifty-four eyes (28 patients) with ROP were included. Twenty-nine eyes (15 patients) received IVC, and 25 eyes (13 patients) received IVR. For infants of the IVC group, the mean gestational age, birth weight, and postmenstrual age (PMA) at the initial treatment were 28.96 ± 2.36 weeks, 1168.8 ± 344.5 g, and 41.22 ± 4.39 weeks, respectively. For the IVR group, they were 28.83 ± 2.34 weeks, 1255.0 ± 356.9 g, and 39.42 ± 2.77 weeks, respectively (P=0.817, 0.522, and 0.075). For the IVC group, FA performed at 71.29–115.43 weeks PMA showed 96.55% of eyes had avascular zone; vascular leakage was found in 24.14% eyes; vascular blunting, vascular dilation, vascular loops, arteriovenous shunt, and capillary dropout were found in 96.55%, 72.41%, 79.31%, 48.28%, and 68.97% eyes, respectively. For the IVR group, FA performed at 65.57–133.71 weeks PMA showed 92.0% of eyes had avascular zone; vascular leakage was found in 40.0% eyes; vascular blunting, dilatation, loops, arteriovenous shunt, and capillary dropout were found in 100%, 60.0%, 64.0%, 36.0%, and 68.0% eyes, respectively. Conclusion No significant difference can be observed between the IVC group and IVR group for peripheral vascular structure anomalies with FA evidence. FA studies should be considered to assess the status of the peripheral retinal vasculature to determine therapeutic outcomes and potential functional outcomes.

Fluorescein angiography of retinal vascular involution after intravitreal injection of ranibizumab for retinopathy of prematurity.

To describe the involution patterns of vessel growth of retina through fluorescein angiography (FA) of children, who had been under treatment up to 1y previously intravitreal ranibizumab (IVR) as monotherapy for retinopathy of prematurity (ROP). This is a retrospective study. The medical information and FA of 17 children (34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters (DD) were analyzed. Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts (100%, 34/34 eyes). Popcorn abnormalities were found in most of the eyes (94.1%, 32/34 eyes). Furthermore, in many cases (23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes (5.9%) showed damage of retinal capillary bed and 3 eyes (8.8%) showed large area of retinal pigment epithelium (RPE) atrophy. Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.

Intravitreal ranibizumab versus laser photocoagulation for retinopathy of prematurity: efficacy, anatomical outcomes and safety

Background/AimsTo compare the efficacy, anatomical outcomes and complications of intravitreal ranibizumab with those of laser photocoagulation for retinopathy of prematurity (ROP).MethodsThis is a retrospective case series of 314 eyes from...

Efficacy of Primary Intravitreal Ranibizumab for Retinopathy of Prematurity in China

Efficacy of Primary Intravitreal Ranibizumab for Retinopathy of Prematurity in China

Serum concentrations of vascular endothelial growth factor in an infant treated with ranibizumab for retinopathy of prematurity

Editor, Vascular endothelial growth factor (VEGF) is considered to be the major growth factor mediating retinal vascularization in retinopathy of prematurity (ROP). Intravitreal anti-VEGF treatment with bevacizumab has been shown to be effective in treating ROP in the BEAT-ROP trial (Mintz-Hittner et al. 2011). However, bevacizumab escapes from the vitreous into the general circulation and reduces systemic VEGF concentrations for weeks to months (Lee et al. 2011; Sato et al. 2012). Thus, there are concerns about systemic complications, particularly in infants with a very low body weight and rapidly developing tissues. Ranibizumab is an alternative anti-VEGF antibody with similar efficacy as bevacizumab but with the advantage that it does not alter systemic VEGF levels in adults (Carneiro et al. 2012). In ROP treatment, ranibizumab has rarely been used. We present a case report of a very premature infant with ROP that received ranibizumab injections in both eyes. We assessed the effect of ranibizumab on the VEGF concentration in the serum. A male infant born at a gestational age of 22+5 weeks and a body weight at birth of 305 g presented with ROP stage 3 in all quadrants in zones 1–2 with plus disease in both eyes. No tractional retinal detachment or vitreous haemorrhage was present. At the time of diagnosis, the infant was in the 33rd gestational week. Because the avascular zone was located at the border of zones 1 and 2, an intravitreal anti-VEGF therapy with 0.2 mg ranibizumab was chosen for both eyes under local anaesthesia. The parents gave written informed consent on the off-label use of the drug. Plasma samples for routine laboratory tests were collected preoperatively, as well as 1 week, 3 weeks and 4 weeks postoperatively. For safety monitoring, serum VEGF levels were determined by multiplex bead analysis (Luminex, Austin, TX, USA). The procedure did not require approval by the local ethics committee. Three days postoperatively, the plus disease had resolved in both eyes. After one week, regular vascularization of the former avascular area had begun and proceeded in the later course. No tractional retinal detachment and no retinal haemorrhage occurred. Systemic VEGF level was 170.9 pg/ml preoperatively. Postinjection of ranibizumab, systemic VEGF levels were 67.3 pg/ml, 0 pg/ml and 205.8 pg/ml at 1 week, 3 weeks and 4 weeks, respectively (Fig. 1). The detection limit of our assay was <2 pg/ml. Serum VEGF levels pre- and post bilateral intravitreal injection of ranibizumab. Serum VEGF levels decrease post bilateral injection of 0.2 mg of ranibizumab reaching a nadir around 2 weeks and return to normal levels 4 weeks after injection. Abbreviations: inj., intravitreal injection; VEGF, vascular endothelial growth factor; wk, week. In this infant, ranibizumab suppressed systemic VEGF levels below detection limit for about 2 weeks reaching a nadir at 2–3 weeks after intravitreal injection. This suppression may be due to an impaired blood–retinal barrier at this age as ranibizumab does not change systemic VEGF levels in adults (Carneiro et al. 2012). A case series of 11 eyes treated with intravitreal bevacizumab for ROP reported a suppression of systemic VEGF levels for at least 7 weeks postinjection (Lee et al. 2011). In contrast, we show that 4 weeks after bilateral injection of ranibizumab, systemic VEGF has returned to normal levels again. Our data suggest that intravitreal ranibizumab also suppresses systemic VEGF, and therefore systemic side effects cannot be excluded. If anti-VEGF treatment is considered, ranibizumab may be the better choice, as systemic VEGF suppression seems to be shorter than with bevacizumab.