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      COMPARISON OF INTRAVITREAL INJECTION OF RANIBIZUMAB VERSUS LASER THERAPY FOR ZONE II TREATMENT-REQUIRING RETINOPATHY OF PREMATURITY

      research-article
      , MD, PhD * , , , MD, MSc * , , MD * , , MBChB, MSc , , MD * , , MMSc * , , MMSc * , , MD * , , MD , , MD * , , BN * , , BN * , , MNurs * , , MSc § , Shenzhen Screening for Retinopathy of Prematurity Cooperative Group
      Retina (Philadelphia, Pa.)
      Retina
      retinopathy of prematurity, ranibizumab, laser therapy, recurrence

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          Abstract

          Through a prospective, randomized, controlled single-center trial, we compare the efficacy and recurrence rates of intravitreal injection of ranibizumab (IVR) versus laser therapy for the Zone II treatment-requiring retinopathy of prematurity and found IVR might not be suitable as a single-dose monotherapy for this disease.

          Abstract

          Purpose:

          To compare the efficacy of intravitreal injection of ranibizumab (IVR) monotherapy and laser therapy for treatment-requiring retinopathy of prematurity (ROP) in Zone II.

          Methods:

          A prospective, randomized, controlled single-center trial was applied from January 2014 to December 2014; infants who were diagnosed as Zone II treatment-requiring ROP (i.e., Zone II Stage 2 or 3 ROP with plus disease) were randomly assigned to receive IVR monotherapy or laser therapy, and the follow-up interval was at least 6 months. Any eyes that developed recurrence of ROP underwent crossover re-treatment.

          Results:

          A total of 100 eyes of 50 ethnic Han Chinese infants were enrolled. At the last follow-up, 26 eyes of 13 infants developed recurrence of ROP in the IVR group and 2 eyes of 1 infant developed recurrence of ROP in the laser therapy group. There was a significant statistical difference in the rate of ROP recurrence between IVR and laser therapy to treat Zone II treatment-requiring ROP ( P = 0.001).

          Conclusion:

          Although IVR appears to regress ROP to certain levels and continue to promote the vascularization of peripheral retinal vessels, a substantial proportion of infants developed recurrence of ROP after a single-dose IVR. Therefore, IVR is not recommended as a single-dose monotherapy for Zone II treatment-requiring ROP.

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          Most cited references24

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          Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial.

          To determine whether earlier treatment using ablation of the avascular retina in high-risk prethreshold retinopathy of prematurity (ROP) results in improved grating visual acuity and retinal structural outcomes compared with conventional treatment. Infants with bilateral high-risk prethreshold ROP (n = 317) had one eye randomized to early treatment with the fellow eye managed conventionally (control eye). In asymmetric cases (n = 84), the eye with high-risk prethreshold ROP was randomized to early treatment or conventional management. High risk was determined using a model based on the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity natural history cohort. At a corrected age of 9 months, visual acuity was assessed by masked testers using the Teller acuity card procedure. At corrected ages of 6 and 9 months, eyes were examined for structural outcome. Outcomes for the 2 treatment groups of eyes were compared using chi2 analysis, combining data for bilateral and asymmetric cases. Grating acuity results showed a reduction in unfavorable visual acuity outcomes with earlier treatment, from 19.5% to 14.5% (P =.01). Unfavorable structural outcomes were reduced from 15.6% to 9.1% (P<.001) at 9 months. Further analysis supported retinal ablative therapy for eyes with type 1 ROP, defined as zone I, any stage ROP with plus disease (a degree of dilation and tortuosity of the posterior retinal blood vessels meeting or exceeding that of a standard photograph); zone I, stage 3 ROP without plus disease; or zone II, stage 2 or 3 ROP with plus disease. The analysis supported a wait-and-watch approach to type 2 ROP, defined as zone I, stage 1 or 2 ROP without plus disease or zone II, stage 3 ROP without plus disease. These eyes should be considered for treatment only if they progress to type 1 or threshold ROP. Early treatment of high-risk prethreshold ROP significantly reduced unfavorable outcomes to a clinically important degree. Additional analyses led to modified recommendations for the use of peripheral retinal ablation in eyes with ROP. Long-term follow-up is being conducted to learn whether the benefits noted in the first year after birth will persist into childhood.
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            Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity.

            Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age. We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P=0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P=0.003) but not for zone II disease (P=0.27). Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).
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              Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity.

              Retinopathy of prematurity (ROP) is initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina of the premature newborn. We propose that vessel regression is a consequence of hyperoxia-induced withdrawal of a critical vascular survival factor. We show that regression of retinal capillaries in neonatal rats exposed to high oxygen, is preceded by a shut-off of vascular endothelial growth factor (VEGF) production by nearby neuroglial cells. Vessel regression occurs via selective apoptosis of endothelial cells. Intraocular injection of VEGF at the onset of experimental hyperoxia prevents apoptotic death of endothelial cells and rescues the retinal vasculature. These findings provide evidence for a specific angiogenic factor acting as a vascular survival factor in vivo. The system also provides a paradigm for vascular remodelling as an adaptive response to an increase in oxygen tension and suggests a novel approach to prevention of ROP.
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                Author and article information

                Journal
                Retina
                Retina (Philadelphia, Pa.)
                retina
                Retina (Philadelphia, Pa.)
                Retina
                0275-004X
                1539-2864
                April 2017
                07 April 2017
                : 37
                : 4
                : 710-717
                Affiliations
                [* ]Pediatric Retinal Surgery Department, Shenzhen Eye Hospital, Shenzhen Key Ophthalmic Laboratory, The Second Affiliated Hospital of Jinan University, Shenzhen, China;
                []Department of Ophthalmology, Royal Free Hospital, London, United Kingdom;
                []Department of Ophthalmology, Kunming City Women and Children Health Hospital, Kunming, China; and
                [§ ]Department of Monitor and Assess, Shenzhen Health Education and Promotion Center, Shenzhen, China.
                Author notes
                Reprint requests: Zhang Guo-ming, MD, PhD, Shenzhen Eye Hospital, Shenzhen Key Ophthalmic Laboratory, The Second Affiliated Hospital of Jinan University, 18 Zetian Road, Shenzhen 518040, China; e-mail: zhang-guoming@ 123456163.com
                Article
                Retina-215-2250 00016
                10.1097/IAE.0000000000001241
                5388026
                27529839
                95001ca4-f2f7-4682-ae69-9f72ed239e5d
                Copyright @ 2016

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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                retinopathy of prematurity,ranibizumab,laser therapy,recurrence

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