Ocular complications following intravitreal bevacizumab injection for retinopathy of prematurity and assessment of risk factors

Abstract

Purpose: Laser ablation of the avascular peripheral retina has been the standard method of ROP treatment. Intravitreal anti-VEGF is useful in the management of ROP patients, especially for aggressive posterior ROP. However, ocular and systemic complication after intravitreal bevacizumab was the main concern. This study aimed to investigate the treatment-related ocular and systemic complications of intravitreal bevacizumab (IVB) in patients with retinopathy of prematurity (ROP).

Method: This retrospective study included neonates receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) to treat ROP. Medical records of the patients were evaluated about the ocular complications after receiving IVB from 2012 to 2019. Treatment-related complications (vitreous hemorrhage, glaucoma, cataract, hyphema, corneal abrasion/opacity, and endophthalmitis), and disease-progression signs including retinal fold or stage 4 or 5 detachment were documented. Any reports of systemic events after injections were also recorded.

Result: Mean gestational age and birth weight of 441 patients receiving IVB for type-1 ROP were 28 ± 2 (22-34 weeks) and 1121 ± 312 (550-2700 g), respectively. The median follow-up after treatment in all patients and patients with complications was 289.43 ± 257 days (5-1899 days) and 385.89 ± 311.59 (196-1192) days, respectively. Out of 865 eyes, 20 eyes (2.31%, 95% Clopper-Pearson Confidence Interval: 1.14-3.54%) have been affected by ocular complications. The rates of different complications included progression of retinopathy in 17 eyes (1.96%), cataracts in 2 eyes (0.23%), and vitreous hemorrhage in one eye (0.11%). No cases of endophthalmitis, thromboembolic events, or death occurred in this study. We evaluated the prevalence ratio (PR) on the multiple risk factors to determine the prediction of the complications. The existence of neovascularization of iris has the highest susceptibility to predict the complication (PR = 5.091, P-value 0.014) following by the presence of retinopathy in zone 1 of the infant's retina (PR = 4.386, P-value = 0.010).

Conclusion: The incidence rate of complications related to Intravitreal bevacizumab injection was low, which was compatible with previous studies. Bevacizumab injection seems well tolerated in most cases of ROP. Iris neovascularization and the presence of retinopathy in zone 1 were associated with a higher occurrence of complications than the absence of these risk factors.

Fig. 1

Left eye of a patient (gestational age: 28 weeks, birth weight: 1000 g) with retinopathy of prematurity (a and b: zone 1, stage3 confluent intravitreal neovascularization and plus disease). Intravitreal Bevacizumab was injected in this eye. The plus disease was improved significantly (c), and neovascularization also reduced. The traction increased in the supranasal part of the retina (d). Laser photocoagulation of the avascular area was done (e and f), and the traction increased 7 weeks after laser (g). Re-injection of intravitreal Bevacizumab was performed. Parents of the patient have not accepted vitrectomy. Finally, the crunch phenomenon occurred (h)