Refractive errors in premature infants with retinopathy of prematurity after anti-vascular endothelial growth factor (anti-VEGF) therapy

Milena S. Vujanović; Gordana Lj. Stanković-Babić; Ana Oros; Gordana D. Zlatanović; Predrag Jovanović; Sonja P. Cekić; Branislav Tomašević; Jasmina M. Djorđević-Jocić

doi:10.2298/VSP150831191V

Milena S. Vujanović Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia
Gordana Lj. Stanković-Babić Faculty of Medicine, University of Niš, Niš, Serbia
Ana Oros Clinic for Eye Diseases, Clinical Center of Vojvodina, Novi Sad, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
Gordana D. Zlatanović Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia
Predrag Jovanović Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia
Sonja P. Cekić Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia
Branislav Tomašević Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia
Jasmina M. Djorđević-Jocić Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia

DOI: https://doi.org/10.2298/VSP150831191V

Keywords: retinopathy of prematurity, refraction, ocular, diagnostic techniques and procedures, myopia, astigmatism, vascular endothelial growth factors,

Abstract

Background/Aim. Retinopathy of prematurity (ROP) is a vasoproliferative retinopathy which affects the blood vessels of the retina during its development. The aim of this study was to evaluate the incidence and the degree of refractive errors in premature infants with severe ROP treated with anti-vascular endothelial growth factor (anti-VEGF) (bevacizumab). Methods. This prospective study included 21 patients (42 eyes) nine months old who received intravitreal injection of anti-VEGF therapy. The control group consisted of 45 patients (90 eyes) who were subjected to laser treatment. In cycloplegia each patient underwent retinoscopy, keratorefractometry, and A-scan ultrasonography. Results. Myopia was present in 47.62% of the eyes in the study group and in 33.33% of the eyes in the control group, but there were no statistically significant differences between these groups. Seven (16.67%) eyes in the study group and 17 (18.89%) eyes in the control group were discovered to have high myopia (SE–spherical equivalents < -3.0 D – dioptre). Clinically significant hypermetropia was higher in the study group (47.62%) than in the control group (34.44%), but with no statistically significant difference. In addition, high hypermetropia was significantly greater in the control group (15.56%) than in the study group (11.90%) (p < 0.001). Astigmatism was more common in the control group than in the study group (81.11% vs 71.43%, respectively), especially high astigmatism (56% vs 43%, respectively). Also the more common form of astigmatism was with the rule (WTR) both in the study and the control group (42.86% vs 55.56%, respectively). Anisometropia was significantly greater in the control group (24.44%) than in the study group (9.52%) (p < 0.05). The children from the study group had significantly greater lens thickness, and a shorter anterior chamber depth than children from the control group (p < 0.01). There was no significant difference in the axial length of the eye between the groups. Conclusion. At the 9-month follow-up myopia was present in the patients with severe ROP treated with anti-VEGF, but high myopia was present to a lesser degree than in the laser treated patients. This difference is possibly related to anterior segment development. Research into the longer-term refractive outcomes is necessary with observation of the biometric components, visual acuity, and the visual field in order to monitor the real effects of this therapy.

Author Biographies

Milena S. Vujanović, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia

ophthalmologist, MD

Gordana Lj. Stanković-Babić, Faculty of Medicine, University of Niš, Niš, Serbia

ophthalmologist, PhD

Ana Oros, Clinic for Eye Diseases, Clinical Center of Vojvodina, Novi Sad, Serbia; Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

ophthalmologist, PhD

Gordana D. Zlatanović, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia

ophthalmologist, PhD

Predrag Jovanović, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia

ophthalmologist, PhD

Sonja P. Cekić, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia

ophthalmologist, PhD

Branislav Tomašević, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia

ophthalmologist, MD

Jasmina M. Djorđević-Jocić, Clinic for Eye Diseases, Clinical Center Niš, Niš, Serbia; Faculty of Medicine, University of Niš, Niš, Serbia

ophthalmologist, PhD

References

Karna P, Muttineni J, Angell L, Karmaus W. Retinopathy of pre-maturity and risk factors: A prospective cohort study. BMC Pediatr 2005; 5(1): 18.

Higgins R. 50 years ago in the journal of pediatrics: Incidence of retrolental fibroplasis: past and present. J Pediatr 2009; 148: 6.

Keshet E. Preventing pathological regression of blood vessels. J Clin Invest 2003; 112(1): 27−9.

Olujic M, Oros A, Bregun-Doronjski A, Velisavljev-Filipovic G. Fac-tors given by birth and oxygenotherapy in relation to devel-opment of retinopathy of prematurity. Med Pregl 2012; 65(7−8): 326−30.

Chen T, Tsai T, Shih Y, Yeh P, Yang C, Hu F, et al. Long-term evaluation of refractive status and optical components in eyes of children born prematurely. Invest Ophthalmol Vis Sci 2010; 51(12): 6140−8.

Gilbert C, Fielder A, Gordillo L, Quinn G, Semiglia R, Visintin P. Characteristics of Infants With Severe Retinopathy of Prema-turity in Countries With Low, Moderate, and High Levels of Development: Implications for Screening Programs. Pediatrics 2005; 115(5): e518−25.

Good WV. The Early Treatment for Retinopathy Of Prematur-ity Study: Structural findings at age 2 years. Br J Ophthalmol 2006; 90(11): 1378−82.

Axer-Siegel R, Maharshak I, Snir M, Friling R, Ehrlich R, Sherf I, et al. Diode laser treatment of retinopathy of prematurity: Ana-tomical and refractive outcomes. Retina (Philadelphia, Pa) 2008; 28(6): 839−46.

Quinn GE, Dobson V, Kivlin J, Kaufman LM, Repka MX, Reynolds JD, et al. Prevalence of myopia between 3 months and 5 1/2 years in preterm infants with and without retinopathy of pre-maturity. Cryotherapy for Retinopathy of Prematurity Cooper-ative Group. Ophthalmology 1998; 105(7): 1292−300.

Quinn GE, Dobson V, Siathowski R, Hardy R, Kilvin J, Palmer E, et al. Does cryotherapy affect refractive error? Results from treated versus control eyes in the cryotherapy for retinopathy of prematurity trial. Ophthalmology 2001; 108(2): 343−7.

Connolly BP, Ng EY, McNamara AJ, Regillo CD, Vander JF, Tas-man W. A comparison of laser photocoagulation with cryothe-rapy for threshold retinopathy of prematurity at 10 years: Part 2. Refractive outcome. Ophthalmology 2002; 109(5): 936−41.

Dhawan A, Dogra M, Vinekar A, Gupta A, Dutta S. Structural sequelae and refractive outcome after successful laser treatment for threshold retinopathy of prematurity. J Pediatr Oph-thalmol Strabismus 2008; 45(6): 356−61.

McLoone EM, Keefe MO, McLoone SF, Lanigan BM. Long-term refractive and biometric outcomes following diode laser thera-py for retinopathy of prematurity. J AAPOS 2006; 10(5): 454−9.

Mintz-Hittner HA, Kennedy KA, Chuang AZ. BEAT-ROP Coop-erative Group . Efficacy of intravitreal bevacizumab for stage 3+retinopathy of prematurity. N Engl J Med. 2011; 364(7): 603−15.

Trese MT. Update on Anti-VEGF Treatment for ROP. Retina Today 2013; 2(8): 57−9.

Harder BC, Baltz S, Schlichtenbrede FC, Jonas JB. Early refractive outcome after intravitreous bevacizumab for retinopathy of prematurity. Arch Ophthalmol 2012; 130(6): 800−1.

Harder BC, Schlichtenbrede FC, Baltz S, Jendritza W, Jendritza B, Jonas JB. Intravitreal bevacizumab for retinopathy of prematur-ity: Refractive error results. Am J Ophthalmol 2013; 155(6): 1119−24.

Section on Ophthalmology American Academy of Pediatrics; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus. Screening ex-amination of premature infants for retinopathy of prematurity. Pediatrics 2006; 117(2): 572−6.

International Committee for the Classification of Retinopathy of Prema-turity. The International Classification of Retinopathy of Pre-maturity revisited. Arch Ophthalmol 2005; 123(7): 991−9.

Good WV. Early Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the Early Treatment for Retinopathy of Prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc 2004; 102: 233−48; discussion 248−50.

Chen YH, Chen SN, Lien RI, Shih CP, Chao AN, Chen KJ, et al. Refractive errors after the use of bevacizumab for the treat-ment of retinopathy of prematurity: 2-year outcomes. Eye (Lond) 2014; 28(9): 1080−6; quiz 1087.

Geloneck MM, Chuang AZ, Clark WL, Hunt MG, Norman AA, Packwood EA, et al. Refractive outcomes following bevacizu-mab monotherapy compared with conventional laser treat-ment: A randomized clinical trial. JAMA Ophthalmol 2014; 132(11): 1327−33.

Hwang CK, Hubbard GB, Hutchinson AK, Lambert SR. Outcomes after Intravitreal Bevacizumab versus Laser Photocoagulation for Retinopathy of Prematurity: A 5-Year Retrospective Analy-sis. Ophthalmology 2015; 122(5): 1008−15.

Martínez-Castellanos MA, Schwartz S, Hernández-Rojas ML, Kon-Jara VA, García-Aguirre G, Guerrero-Naranjo JL, et al. Long-term effect of antiangiogenic therapy for retinopathy of pre-maturity up to 5 years of follow-up. Retina (Philadelphia, Pa.) 2013; 33(2): 329−38.

Repka MX. Refraction and keratometry in premature infants. Br J Ophthalmol 2004; 88(7): 853−4.

Wang J, Ren X, Shen L, Yanni SE, Leffler JN, Birch EE. Devel-opment of refractive error in individual children with regressed retinopathy of prematurity. Invest Ophthalmol Vis Sci 2013; 54(9): 6018−24.

Fledelius HC, Fledelius C. Eye size in threshold retinopathy of prematurity, based on a Danish preterm infant series: Early axial eye growth, pre- and postnatal aspects. Invest Ophthal-mol Vis Sci 2012; 53(7): 4177−84.

Yang CS, Wang AG, Shih YF, Hsu WM. Long-term biometric optic components of diode laser-treated threshold retinopathy of prematurity at 9 years of age. Acta Ophthalmol 2013; 91(4): e276−82.

Davitt BV, Dobson V, Quinn GE, Hardy RJ, Tung B, Good WV, et al. Early Treatment for Retinopathy of Prematurity Cooper-ative Group. Astigmatism in the Early Treatment for Retino-pathy of Prematurity Study: Findings to 3 years of age. Oph-thalmology 2009; 116(2): 332−9.

Davitt BV, Quinn GE, Wallace DK, Dobson V, Hardy RJ, Tung B, et al. Astigmatism progression in the early treatment for reti-nopathy of prematurity study to 6 years of age. Ophthalmolo-gy 2011; 118(12): 2326−9.

Yang CS, Wang AG, Shih YF, Hsu WM. Astigmatism and bio-metric optic components of diode laser-treated threshold reti-nopathy of prematurity at 9 years of age. Eye (Lond) 2013; 27(3): 374−81.