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Need for Revised Screening Protocol for Early Detection of Retinopathy of Prematurity in Infants Born Before 25 Weeks—Reply

Need for Revised Screening Protocol for Early Detection of Retinopathy of Prematurity in Infants... In reply We thank Mireskandari and coworkers for interest in our article.1 Although ROP recurrences after the 54-week BEAT-ROP2 end point were predicted,3,4 our aims were to describe novel reactivation patterns and progression to RD. We described reactivation of persistent ROP, which had not regressed sufficiently after initial treatment, and ROP recurrence after initial regression. We described posterior and anterior reactivation patterns. We reported that no eye treated with laser for reactivation progressed to RD. We suggested close follow-up until either retina vascular termination reaches its normal location near the ora serrata5 or laser treatment is performed. We acknowledge our study to be small, retrospective, and subject to referral bias. Although intravitreal bevacizumab injection has been shown to reduce systemic vascular endothelial growth factor in infants treated with laser for ROP,6 vascular endothelial growth factor levels are abnormally elevated in infants with ROP,7 so their reduction, even with repeated injection, is not necessarily deleterious. It should be noted that the eyes studied by Sato et al6 had previously received laser ablation, which is likely to have increased systemic exposure by reducing the blood-retina barrier. Although infant 9 was outside the normal age and weight range, his neonatologists recommended screening based on systemic health, according to standard criteria.8 Although photographic documentation of initial aggressive posterior ROP unfortunately is not available, an ETROP-certified examiner (M.J.S.) felt the findings were unequivocal. Large babies with aggressive posterior ROP have been described.9 Figure 4 in our article is from 48 weeks' PMA, after several bevacizumab treatments. We believe that closer follow-up and earlier intervention would have led to better outcomes in the eyes with RD. Patient 2 worsened during noncompliance with follow-up. Patients 1 and 8 worsened during extended follow-up after initial apparent stability. Unfortunately, reactivation patterns and timing were not known at that time. Close, long-term follow-up of patients treated with bevacizumab is certainly of utmost concern. We perform injections within 1.0 mm of the limbus but do not have data regarding the location of injection in infants initially treated at other sites. The RDs in our study were tractional, not rhegmatogenous, and related to contraction of extraretinal fibrovascular tissue rather than proliferative vitreoretinopathy. We agree with the need to standardize the definition of reactivation patterns and re-treatment criteria. We hope that our article serves as a starting point. Certainly, there may be eyes with mild reactivation that may not need re-treatment, but in the absence of robust data regarding re-treatment criteria, we suggest treatment when plus disease returns or extraretinal fibrovascular tissue growth is seen, either posteriorly or anteriorly. Additionally, to reduce the follow-up burden and prevent late reactivation, we recommend laser treatment of persistent avascular retina past 60 weeks' PMA since we cannot predict which eyes may have reactivation months (or years) later. Although BEAT-ROP has limitations, it demonstrated a statistically significant advantage for bevacizumab injection for posterior disease. This should not be lost amidst debate regarding long-term surveillance and re-treatment requirement. Back to top Article Information Correspondence: Dr Blair, Retina Consultants, Ltd, 2454 E Dempster St, Ste 400, Des Plaines, IL 60016 (michaelblairmd@gmail.com). Conflict of Interest Disclosures: None reported. References 1. Hu J, Blair MP, Shapiro MJ, Lichtenstein SJ, Galasso JM, Kapur R. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol. 2012;130(8):1000-100622491394PubMedGoogle ScholarCrossref 2. Mintz-Hittner HA, Kennedy KA, Chuang AZ.BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603-61521323540PubMedGoogle ScholarCrossref 3. Moshfeghi DM, Berrocal AM. Retinopathy of prematurity in the time of bevacizumab: incorporating the BEAT-ROP results into clinical practice. Ophthalmology. 2011;118(7):1227-122821724044PubMedGoogle Scholar 4. Blair M, Shapiro MJ. Bevacizumab for ROP. Ophthalmology. 2012;119(2):431-43222305321PubMedGoogle ScholarCrossref 5. Blair MP, Shapiro MJ, Hartnett ME. Fluorescein angiography to estimate normal peripheral retinal nonperfusion in children. J AAPOS. 2012;16(3):234-23722681939PubMedGoogle ScholarCrossref 6. Sato T, Wada K, Arahori H, et al. Serum concentrations of bevacizumab (Avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity. Am J Ophthalmol. 2012;153(2):327-333, e121930258PubMedGoogle ScholarCrossref 7. Villegas-Becerril E, González-Fernández R, Perula-Torres L, Gallardo-Galera JM. IGF-I, VEGF and bFGF as predictive factors for the onset of retinopathy of prematurity (ROP) [in Spanish]. Arch Soc Esp Oftalmol. 2006;81(11):641-64617136637PubMedGoogle ScholarCrossref 8. Section on Ophthalmology, American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity [published corrections appear in Pediatrics. 2006;117(4):1468 and Pediatrics. 2006;118(3):1324]. Pediatrics. 2006;117(2):572-57616452383PubMedGoogle ScholarCrossref 9. Shah PK, Narendran V, Kalpana N. Aggressive posterior retinopathy of prematurity in large preterm babies in South India. Arch Dis Child Fetal Neonatal Ed. 2012;97(5):F371-F37522611114PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Ophthalmology American Medical Association

Need for Revised Screening Protocol for Early Detection of Retinopathy of Prematurity in Infants Born Before 25 Weeks—Reply

JAMA Ophthalmology , Volume 131 (4) – Apr 1, 2013

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Publisher
American Medical Association
Copyright
Copyright © 2013 American Medical Association. All Rights Reserved.
ISSN
2168-6165
eISSN
2168-6173
DOI
10.1001/jamaophthalmol.2013.35
Publisher site
See Article on Publisher Site

Abstract

In reply We thank Mireskandari and coworkers for interest in our article.1 Although ROP recurrences after the 54-week BEAT-ROP2 end point were predicted,3,4 our aims were to describe novel reactivation patterns and progression to RD. We described reactivation of persistent ROP, which had not regressed sufficiently after initial treatment, and ROP recurrence after initial regression. We described posterior and anterior reactivation patterns. We reported that no eye treated with laser for reactivation progressed to RD. We suggested close follow-up until either retina vascular termination reaches its normal location near the ora serrata5 or laser treatment is performed. We acknowledge our study to be small, retrospective, and subject to referral bias. Although intravitreal bevacizumab injection has been shown to reduce systemic vascular endothelial growth factor in infants treated with laser for ROP,6 vascular endothelial growth factor levels are abnormally elevated in infants with ROP,7 so their reduction, even with repeated injection, is not necessarily deleterious. It should be noted that the eyes studied by Sato et al6 had previously received laser ablation, which is likely to have increased systemic exposure by reducing the blood-retina barrier. Although infant 9 was outside the normal age and weight range, his neonatologists recommended screening based on systemic health, according to standard criteria.8 Although photographic documentation of initial aggressive posterior ROP unfortunately is not available, an ETROP-certified examiner (M.J.S.) felt the findings were unequivocal. Large babies with aggressive posterior ROP have been described.9 Figure 4 in our article is from 48 weeks' PMA, after several bevacizumab treatments. We believe that closer follow-up and earlier intervention would have led to better outcomes in the eyes with RD. Patient 2 worsened during noncompliance with follow-up. Patients 1 and 8 worsened during extended follow-up after initial apparent stability. Unfortunately, reactivation patterns and timing were not known at that time. Close, long-term follow-up of patients treated with bevacizumab is certainly of utmost concern. We perform injections within 1.0 mm of the limbus but do not have data regarding the location of injection in infants initially treated at other sites. The RDs in our study were tractional, not rhegmatogenous, and related to contraction of extraretinal fibrovascular tissue rather than proliferative vitreoretinopathy. We agree with the need to standardize the definition of reactivation patterns and re-treatment criteria. We hope that our article serves as a starting point. Certainly, there may be eyes with mild reactivation that may not need re-treatment, but in the absence of robust data regarding re-treatment criteria, we suggest treatment when plus disease returns or extraretinal fibrovascular tissue growth is seen, either posteriorly or anteriorly. Additionally, to reduce the follow-up burden and prevent late reactivation, we recommend laser treatment of persistent avascular retina past 60 weeks' PMA since we cannot predict which eyes may have reactivation months (or years) later. Although BEAT-ROP has limitations, it demonstrated a statistically significant advantage for bevacizumab injection for posterior disease. This should not be lost amidst debate regarding long-term surveillance and re-treatment requirement. Back to top Article Information Correspondence: Dr Blair, Retina Consultants, Ltd, 2454 E Dempster St, Ste 400, Des Plaines, IL 60016 (michaelblairmd@gmail.com). Conflict of Interest Disclosures: None reported. References 1. Hu J, Blair MP, Shapiro MJ, Lichtenstein SJ, Galasso JM, Kapur R. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol. 2012;130(8):1000-100622491394PubMedGoogle ScholarCrossref 2. Mintz-Hittner HA, Kennedy KA, Chuang AZ.BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603-61521323540PubMedGoogle ScholarCrossref 3. Moshfeghi DM, Berrocal AM. Retinopathy of prematurity in the time of bevacizumab: incorporating the BEAT-ROP results into clinical practice. Ophthalmology. 2011;118(7):1227-122821724044PubMedGoogle Scholar 4. Blair M, Shapiro MJ. Bevacizumab for ROP. Ophthalmology. 2012;119(2):431-43222305321PubMedGoogle ScholarCrossref 5. Blair MP, Shapiro MJ, Hartnett ME. Fluorescein angiography to estimate normal peripheral retinal nonperfusion in children. J AAPOS. 2012;16(3):234-23722681939PubMedGoogle ScholarCrossref 6. Sato T, Wada K, Arahori H, et al. Serum concentrations of bevacizumab (Avastin) and vascular endothelial growth factor in infants with retinopathy of prematurity. Am J Ophthalmol. 2012;153(2):327-333, e121930258PubMedGoogle ScholarCrossref 7. Villegas-Becerril E, González-Fernández R, Perula-Torres L, Gallardo-Galera JM. IGF-I, VEGF and bFGF as predictive factors for the onset of retinopathy of prematurity (ROP) [in Spanish]. Arch Soc Esp Oftalmol. 2006;81(11):641-64617136637PubMedGoogle ScholarCrossref 8. Section on Ophthalmology, American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening examination of premature infants for retinopathy of prematurity [published corrections appear in Pediatrics. 2006;117(4):1468 and Pediatrics. 2006;118(3):1324]. Pediatrics. 2006;117(2):572-57616452383PubMedGoogle ScholarCrossref 9. Shah PK, Narendran V, Kalpana N. Aggressive posterior retinopathy of prematurity in large preterm babies in South India. Arch Dis Child Fetal Neonatal Ed. 2012;97(5):F371-F37522611114PubMedGoogle ScholarCrossref

Journal

JAMA OphthalmologyAmerican Medical Association

Published: Apr 1, 2013

References

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