Sarkhan ELBAYİYEV, Özdemir ÖZDEMİR, Burak CERAN, Mustafa Şenol AKIN, Fuat Emre CANPOLAT, Suna OGUZ

İntravitreal Bevacizumab Uygulanan Prematüre Retinopatisi Olan Bebeklerin Değerlendirilmesi

Amaç: Agresif posterior prematüre retinopatisi olan prematüre bebeklerde intravitreal bevacizumab enjeksiyonunun sistemik, lokal etkilerini ve yan etkilerini değerlendirmek. Gereç ve Yöntemler: Haziran 2020 ile Mart 2021 arasında tek merkezli gözlemsel kohort çalışmasına toplam 16 hasta dahil edildi. Toplam 32 göz için intravitreal 0.3 mg bevacizumab enjeksiyonu öncesi ve sonrası klinik, laboratuvar ve radyolojik bulgular kaydedildi. Bulgular: Hastaların doğumdaki ortalama gestasyonel yaşı 25±0.38 hafta ve ortalama doğum ağırlığı 695±119.2 gr’dı. Hiçbir hastada postmenstrüel 34 haftalıkken intravitreal enjeksiyona sekonder lokal vitreus kanaması veya endoftalmit gibi komplikasyonlar gelişmedi, hiçbirinde tekrarlanan enjeksiyon gerekmedi. Enjeksiyondan sonra intraventriküler kanama oranında artış olmadı. Tedavi öncesi ve sonrası hastaların laboratuvar parametreleri, kan basıncı değerleri veya sistemik bulguları arasında istatistiksel olarak anlamlı bir fark yoktu. Sonuç: Bu çalışmada intravitreal bevacizumab enjeksiyonu ile tedavi edilen hastalarda sistemik veya lokal yan etki görülmemekle birlikte hastalar sistemik hipertansiyon, intraventriküler kanama ve hipotansiyon açısından yakından izlenmelidir. Diğer tedavi seçeneklerine kıyasla daha sonraki nörogelişimsel sonuçları değerlendirmek için daha ayrıntılı çalışmalara ihtiyaç vardır.

Anahtar Kelimeler:

Bevacizumab, İntraventriküler kanama, Hipotansiyon, Hipertansiyon, Prematüre Retinopatisi

Evaluation of Infants with Retinopathy of Prematurity Treated with Intravitreal Bevacizumab

Objective: To evaluate the systemic and local effects and side effects of intravitreal bevacizumab injection in preterm infants with aggressive posterior retinopathy of prematurity. Material and Methods: A total of 16 patients were included in this single-center observational cohort study between June 2020 and March 2021. The clinical, laboratory, and radiological findings before and after intravitreal injection of 0.3 mg bevacizumab were recorded for a total of 32 eyes. Results: The patients’ mean gestational age at birth was 25±0.38 weeks and their mean birth weight was 695±119.2 g. None of the patients developed complications such as local vitreous hemorrhage or endophthalmitis secondary to intravitreal injection administered at a postmenstrual age of 34 weeks, and none required repeated injections. There was no increase in the rate of intraventricular hemorrhage after injection. There was no statistically significant difference in the patients’ laboratory parameters, blood pressure values, or systemic findings before and after treatment. Conclusion: Although no systemic or local side effects were observed in patients treated with intravitreal bevacizumab injection in this study, patients should be monitored closely for systemic hypertension, intraventricular hemorrhage, and hypotension. More detailed studies are needed to evaluate later neurodevelopmental outcomes compared to other treatment options.

Keywords:

Bevacizumab, Intraventricular hemorrhage, Hypotension, Hypertension, Retinopathy of Prematurity,

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Bas AY, Koc E, Dilmen U. Incidence and severity of retinopathy of prematurity in Turkey. Br J Ophthalmol 2015;99:1311-4.
Bas AY, Demirel N, Koc E, Ulubas Isik D, Hirfanoglu İ M, Tunc T. Incidence, risk factors and severity of retinopathy of prematurity in Turkey (TR-ROP study): a prospective, multicentre study in 69 neonatal intensive care units. Br J Ophthalmol 2018;102:1711-6.
International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005;123:991-9.
Gunay M, Sukgen EA, Celik G, Kocluk Y. Comparison of Bevacizumab, Ranibizumab, and Laser Photocoagulation in the Treatment of Retinopathy of Prematurity in Turkey. Curr Eye Res 2017;42:462-9.
Blair M, Gonzalez JMG, Snyder L, Schechet S, Greenwald M, Shapiro M, et al. Bevacizumab or laser for aggressive posterior retinopathy of prematurity. Taiwan J Ophthalmol 2018;8:243-8.
Wu LH, Yang YH, Lin CH, Lin YJ, Cheng CL. Hypotension Associated With Intravitreal Bevacizumab Therapy for Retinopathy of Prematurity. Pediatrics 2016;137:e20152005.
Twitty G, Weiss M, Albayram MS, O’Mara K, Mowitz ME. Hypertension and Neuroimaging Changes After Bevacizumab for Retinopathy of Prematurity. Pediatrics 2020;145: e20191814.
Sweet DG, Carnielli V, Greisen G, Hallman M, Ozek E, Te Pas A, et al. European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update. Neonatology 2019;115:432-50.
Mitra S, Florez ID, Tamayo ME, Aune D, Mbuagbaw L, Veroniki AA, et al. Effectiveness and safety of treatments used for the management of patent ductus arteriosus (PDA) in preterm infants: a protocol for a systematic review and network meta-analysis. BMJ open 2016;6:e011271.
Camacho-Gonzalez A, Spearman PW, Stoll BJ. Neonatal infectious diseases: evaluation of neonatal sepsis. Pediatr Clin North Am 2013;60:367-89.
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann surg 1978;187:1-7.
Parodi A, Govaert P, Horsch S, Bravo MC, Ramenghi LA. Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome. Pediatr Res 2020;87:13-24.
Fierson WM. Screening examination of premature infants for retinopathy of prematurity. Pediatrics 2013;131:189-95.
Quimson SK. Retinopathy of Prematurity: Pathogenesis and Current Treatment Options. Neonatal Netw 2015;34:284-7.
Rathi S, Jalali S, Patnaik S, Shahulhameed S, Musada GR, Balakrishnan D, et al. Abnormal Complement Activation and Inflammation in the Pathogenesis of Retinopathy of Prematurity. Front Immunol 2017;8:1868.
Chang JW. Risk factor analysis for the development and progression of retinopathy of prematurity. PloS one 2019;14:e0219934.
Lee JW, McElrath T, Chen M, Wallace DK, Allred EN, Leviton A, et al. Pregnancy disorders appear to modify the risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia. J Matern Fetal Neonatal Med 2013;26:811-8.
Anaya-Alaminos R, García-Serrano JL, Cantero-Hinojosa J. Prenatal and postnatal factors increase risk of severe ROP. J Matern Fetal Neonatal Med 2014;27:635-6.
Wang X, Tang K, Chen L, Cheng S, Xu H. Association between sepsis and retinopathy of prematurity: a systematic review and meta-analysis. BMJ open 2019;9:e025440.
Villamor-Martinez E, Cavallaro G, Raffaeli G, Mohammed Rahim OMM, Gulden S, Ghazi AMT, et al. Chorioamnionitis as a risk factor for retinopathy of prematurity: An updated systematic review and meta-analysis. PloS one 2018;13:e0205838.
Visser L, Singh R, Young M, Lewis H, McKerrow N. Guideline for the prevention, screening and treatment of retinopathy of prematurity (ROP). S Afr Med J 2012;103:116-25.
Lin L, Binenbaum G. Postnatal weight gain and retinopathy of prematurity. Semin Perinatol 2019;43:352-9.
Hartnett ME. Advances in understanding and management of retinopathy of prematurity. Surv Ophthalmol 2017;62:257-76.
Ahn YJ, Hong KE, Yum HR, Lee JH, Kim KS, Youn YA, et al. Characteristic clinical features associated with aggressive posterior retinopathy of prematurity. Eye (Lond) 2017;31:924-30.
Gupta MP, Yonekawa Y, Campbell JP, Rusu I, Zahid S, Patel SN, et al. Early Diagnosis and Management of Aggressive Posterior Vitreoretinopathy Presenting in Premature Neonates. Ophthalmic Surg Lasers Imaging Retina 2019;50:201-7.
Sankar MJ, Sankar J, Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst Rev 2018;1:CD009734.
Kara C, Hekimoglu E, Petricli IS, Akil H. Intravitreal bevacizumab as rescue therapy following treatment failure with laser photocoagulation in retinopathy of prematurity. J Curr Ophthalmol 2018;30:80-4.
Tandon M, Vishal MY, Kohli P, Rajan RP, Ramasamy K. Supplemental Laser for Eyes Treated with Bevacizumab Monotherapy in Severe Retinopathy of Prematurity. Ophthalmol Retina 2018;2:623-8.
Bazvand F, Riazi-Esfahani H, Mirshahi A, Khodabande A, Khojastheh H, Farahani AD, et al. Ocular complications following intravitreal bevacizumab injection for retinopathy of prematurity and assessment of risk factors. Int J Retina Vitreous 2021;7:5.
Shoeibi N, Hosseini SM, Banaee T, Ansari-Astaneh MR, Abrishami M, Ahmadieh H. Vitreous changes after intravitreal bevacizumab monotherapy for retinopathy of prematurity: a case series. Int J Retina Vitreous 2018;4:10.
Kang HG, Choi EY, Byeon SH, Kim SS, Koh HJ, Lee SC, et al. Anti-vascular Endothelial Growth Factor Treatment of Retinopathy of Prematurity: Efficacy, Safety, and Anatomical Outcomes. Korean J Ophthalmol 2018;32:451-8.
Popovic MM, Nichani P, Muni RH, Mireskandari K, Tehrani NN, Kertes PJ. Intravitreal antivascular endothelial growth factor injection versus laser photocoagulation for retinopathy of prematurity: A meta-analysis of 3,701 eyes. Surv Ophthalmol 2021;66:572-84.
Wang SD, Zhang GM, Shenzhen Screening for Retinopathy of Prematurity Cooperative G. Laser therapy versus intravitreal injection of anti-VEGF agents in monotherapy of ROP: a Meta-analysis. Int J Ophthalmol 2020;13:806-15.
Frosini S, Franco F, Vicini G, Nicolosi C, Varriale G, Dani C, et al. Efficacy and safety of intravitreal bevacizumab for the treatment of retinopathy of prematurity: a single-center retrospective review. J
Matern Fetal Neonatal Med 2020:1-6. doi: 10.1080/14767058.2020.1818214.
Gunay M, Celik G, Gunay BO, Aktas A, Karatekin G, Ovali F. Evaluation of 2-year outcomes following intravitreal bevacizumab (IVB) for aggressive posterior retinopathy of prematurity. Arq Bras Oftalmol 2015;78:300-4.
Nicoara SD, Nascutzy C, Cristian C, Irimescu I, Stefanut AC, Zaharie G, et al. Outcomes and Prognostic Factors of Intravitreal Bevacizumab Monotherapy in Zone I Stage 3+ and Aggressive Posterior Retinopathy of Prematurity. J Ophthalmol 2015;2015:102582.
Eftekhari Milani A, Hassanpoor N, Mousavi Mirkala M, Taheri A, Golizade A, Niyousha MR. Intravitreal bevacizumab injection in aggressive posterior retinopathy of prematurity compared with type I retinopathy of prematurity. Int Ophthalmol 2020;40:477-82.
Tong Q, Yin H, Zhao M, Li X, Yu W. Outcomes and prognostic factors for aggressive posterior retinopathy of prematurity following initial treatment with intravitreal ranibizumab. BMC Ophthalmol 2018;18:150. doi: 10.1186/s12886-018-0815-1.
Dikci S, Ceylan OM, Demirel S, Yilmaz T. Which dose of bevacizumab is more effective for the treatment of aggressive posterior retinopathy of prematurity: lower or higher dose? Arq Bras Oftalmol 2018;81:12-7.