Intravitreal Ranibizumab Injection for Aggressive Versus Type 1 Prethreshold Retinopathy of Prematurity

A prospective randomized study of 37 eyes of 30 infants, who received intravitreal injections of ranibizumab in one eye (the most severe) or both eyes, were included. A-ROP group included 18 eyes of 15 infants and type 1 ROP group included 19 eyes of 15 infants. The primary outcome measure was the number of eyes that achieved regression of ROP without additional treatment till 55 weeks' post-menstrual age (PMA). The mean follow-up period for A-ROP group was 11.44 months and 13.95 months for type 1 ROP group.

Treatment was performed within 72 hours once treatment criteria were detected. Intravitreal injection (IVI) was performed under topical anesthesia in standard ophthalmic operating room. 5% povidone-iodine disinfection and topical antibiotic were instilled. Ranibizumab (0.25 mg/0.025 mL) was injected into the vitreous cavity with a 31-gauge needle, aiming the needle directly toward the optic nerve in direction of visual axis 1.0 mm posterior to the corneoscleral junction at the inferotemporal quadrant. The intraocular pressure and central artery perfusion were then checked. Topical antibiotics were given for 7 days postoperatively. All infants were followed up on the next day, third day, then weekly until the regression of ROP, after that every (2-4) weeks until a minimum of 55 weeks' post menstrual age (PMA) or retinal vascularization achieved zone III without an active component such as hemorrhage or exudation or clinically significant tractional elements, which came earlier. Each examination evaluated disease regression (via indirect fundoscopic analysis), recurrence, the presence of tractional elements and peripheral vascularization. Then follow up was continued monthly for at least 6 months following treatment.

Successful treatment was defined as remission of plus disease, good pupil dilation and reduced disease grade. Outcomes were further classified as insufficient regression (persistence of plus disease and neovascularization at 3-5 days' post-injection), progression (post-injection intravitreal hemorrhage, increased neovascularization and formation of tractional components) and recurrence requiring treatment (recurrence of plus disease, recurrent neovascularization, reformation of a ridge or extraretinal fibrovascular proliferation, despite initial regression post injection) Once insufficient regression or ROP recurrence requiring treatment was determined, rescue therapy of IVR was applied.

Cases with no recurrence or recurrence not requiring treatment (stage 1 or 2 eyes, with Zone 2 or Zone 3 localisation, not accompanied by plus disease) were closely monitored until peripheral retinal vascularization was completed.

In case of failed peripheral retinal vascularization to approach zone III until 55 weeks' PMA, an indirect infrared diode laser (IRIDEX, Iris Medical SL laser with laser indirect ophthalmoscope (LIO) Ophthalmic Laser, 810 nm, USA) was used to apply photocoagulation through a +20/+28 diopter condensing lens under sedation or general anesthesia in the operating room to reduce the risk of late ROP reactivation.

Follow-up examinations were made weekly for the first month after laser photocoagulation and at 3-4-week intervals thereafter until the ROP findings receded. Follow-up examinations were continued at 3-4-month intervals after the patients turned 1-year old.

Inclusion criteria

• Infants with a birth weight of ≤ 1500 g or gestational age of ≤ 30 weeks and selected infants with birth weight between 1500 and 2000 g or gestational age of more than 30 weeks with an unstable clinical course, including those requiring cardiorespiratory support.
• Infants with type 1 ROP, as defined by the ETROP study 11, Zone 1, any stage ROP with plus disease; Zone 1, stage 3 ROP with or without plus disease; Zone 2, stage 2 or 3 ROP with plus disease( affecting either one or both eyes).
• Aggressive ROP (A-ROP), according to the International Classification of ROP (ICROP) criteria affecting either one or both eyes.

Exclusion criteria

• Eyes with previous intravitreal injections.
• Eyes with previous laser therapy.
• Eyes with any other pathology, other than ROP.
• Eyes with ROP stage 4 or 5.