Outcomes and prognostic factors for aggressive posterior retinopathy of prematurity following initial treatment with intravitreal ranibizumab

Abstract

BackgroundThis study sought to identify factors associated with retinal detachment and retreatment of aggressive posterior retinopathy of prematurity (APROP) initially treated with intravitreal ranibizumab (IVR) injection as well as the efficacy of IVR treatment.MethodsThis was a retrospective study. A total of 83 preterm infants (160 eyes) diagnosed with APROP who were primarily treated with IVR were included. The 160 eyes were divided into two groups based on the anatomic outcomes. Group A included 35 eyes that developed retinal detachment, and Group B included 125 eyes without retinal detachment. The following patient factors were retrospectively reviewed: gender, gestational age (GA), birth weight (BW), postmenstrual age (PMA) at first treatment, iris neovascularizations, retinal hemorrhage, neutrophil and lymphocyte counts before the first intravitreal injection, neutrophil-to-lymphocyte ratio (NLR), anatomical outcomes, additional treatment and follow-up time. Three dummy variables were created as dependent variables based on the methods of retreatment. The possible risk factors for APROP were evaluated, and statistical analyses included univariate and multivariate logistic regression.ResultsA total of 160 eyes from 83 preterm infants (56 males and 27 females) underwent initial IVR treatment with a follow-up time of 17.17 ± 10.54 months. Thirty-five of the 160 (21.9%) eyes progressed to retinal detachment, and 82 of the 125 (65.6%) non-retinal detachment eyes needed retreatment, with favorable anatomical outcomes. The disease improved approximately 1.5 ± 1.2 weeks after the first IVR treatment. The mean recurrence period of APROP was approximately 7.5 ± 6.9 weeks after the first IVR treatment. Multiple logistic regression analysis revealed postmenstrual age (P < 0.001) and neutrophil count (P = 0.009) as the most significant factors for retinal detachment in APROP. Retinal hemorrhage (P = 0.007) and BW (P = 0.04) were most significantly associated with APROP recurrence and retreatment.ConclusionsIVR injection is an effective treatment for APROP. In this study, older postmenstrual age and low neutrophil count were identified as risk factors for retinal detachment in APROP. In addition, retinal hemorrhage and low BW were significantly associated with recurrence and retreatment in non-retinal detachment APROP. Thus, patients with a lower BW, older postmenstrual age, low neutrophil count and retinal hemorrhage should be reexamined in a timely and more frequent manner.

<p>Evidence to date: ranibizumab and its potential in the treatment of retinopathy of prematurity</p>

“…Based on ROP classification, recurrence was seen in 70 of 105 (67%) eyes with APROP, 157 of 411 (38%) eyes with type 1 ROP, and 18 of 113 (16%) eyes with prethreshold ROP. Higher rates of recurrence in eyes with APROP have previously been noted in patients receiving either intravitreal ranibizumab34 or bevacizumab44 with low birthweight as a common risk factor for APROP recurrence and retreatment. Feng et al33 also noted that the rate of recurrence was significantly higher in patients with zone I ROP (61%, 101 of 164 eyes) than in zone II ROP (31%, 144 of 465 eyes).…”

“…A recent Cochrane review in 2018 concluded that there was insufficient evidence to provide a strong conclusion for the routine use of intravitreal anti-VEGFs in clinical practice 23. To date, eight head-to-head studies19,24–31 have been published comparing intravitreal ranibizumab to intravitreal bevacizumab and/or conventional laser photocoagulation for ROP and three retrospective studies32–34 with at least 100 eyes have been published on outcomes of infants treated intravitreal ranibizumab monotherapy (Table 2).…”

“…In 2018, Tong et al34 reported outcomes of a retrospective review of 83 infants (160 eyes) with aggressive posterior ROP (APROP) treated with intravitreal ranibizumab (0.25 mg). They noted that 35 of 160 (22%) eyes progressed to retinal detachment and reported older postmenstrual age and low neutrophil count as independent risk factors for retinal detachment in APROP on multivariate analysis.…”

Outcomes of early versus deferred laser after intravitreal ranibizumab in aggressive posterior retinopathy of prematurity

“…Six weeks was taken as the benchmark for deferred laser, as most cases of recurrence or reactivation after initial IVR tend to occur after 6 weeks. [ 13 14 15 ] The infants in group 2 were Followed up weekly to monitor the growth of retinal vessels and recurrence of plus disease or appearance of peripheral retinopathy. The laser was done using Diode laser indirect ophthalmoscope (Iridex ® Germany) under topical anesthesia in NICU after obtaining written informed consent from the parents.…”

“…[ 10 11 12 ] Unfavorable structural outcomes and late recurrence of disease and thus need for longer follow-up are common issues with anti-VEGF monotherapy. [ 10 13 14 15 ] To overcome the disadvantages of conventional laser as well as anti-VEGF monotherapy, combined treatment has been evaluated in infants with Zones I and II ROP, which showed promising anatomical outcomes. [ 12 ] Similarly, outcomes of rescue laser after initial treatment with anti-VEGF therapy had also shown good results in APROP.…”