Intravitreal Ranibizumab for Aggressive Posterior Retinopathy of Prematurity: A Prospective Interventional Case Series

Evaluation of Efficacy & Outcomes of Intra-vitreal Ranibizumab Injection in the Treatment of Aggressive Posterior Retinopathy of Prematurity

Aggressive posterior retinopathy of prematurity (AP-ROP) is a severe form of retinopathy of prematurity that can progress rapidly and lead to retinal detachment and permanent vision loss if not treated promptly. Although laser photocoagulation has traditionally been the standard treatment, intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications such as ranibizumab have emerged as an alternative treatment because they may preserve the developing peripheral retina.

This study was designed to evaluate the effectiveness and safety of intravitreal ranibizumab in premature infants with AP-ROP. The study assessed the initial response to treatment, the frequency and timing of disease reactivation, the need for additional injections, retinal vascularization during follow-up, and treatment-related complications.

The information obtained from this study is intended to improve understanding of the role of ranibizumab in the management of AP-ROP and to guide follow-up strategies for infants receiving anti-VEGF therapy.

Study Overview

• Status: Completed
• Conditions: Retinopathy of Prematurity (ROP)
• Intervention / Treatment: Drug: Intravitreal Ranibizumab injection

Detailed Description

**Detailed Description**

Aggressive posterior retinopathy of prematurity (AP-ROP) is a rapidly progressive and vision-threatening subtype of retinopathy of prematurity (ROP) characterized by prominent plus disease, posterior retinal involvement, and rapid progression to retinal detachment if left untreated. Although laser photocoagulation has long been considered the standard treatment for severe ROP, its application in AP-ROP may be technically challenging because of the posterior location of the disease and is associated with permanent ablation of the peripheral retina, high myopia, and visual field constriction.

Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has emerged as an alternative treatment that promotes rapid regression of retinal neovascularization while preserving peripheral retinal tissue. Ranibizumab is characterized by a shorter systemic and intravitreal half-life than other anti-VEGF agents, which may reduce systemic VEGF suppression but may also be associated with a higher risk of disease reactivation, necessitating prolonged surveillance after treatment.

This prospective interventional study was designed to evaluate the efficacy and safety of intravitreal ranibizumab as primary treatment for AP-ROP. The study aimed to assess the rate and timing of disease regression and reactivation, the need for additional intravitreal injections, retinal vascularization during follow-up, and anatomical outcomes. The study also sought to characterize the morphological patterns of disease reactivation and evaluate treatment-related ocular and systemic complications.

The findings are intended to contribute to the growing body of evidence regarding anti-VEGF therapy for AP-ROP and to provide additional data on long-term disease behavior following ranibizumab treatment in premature infants.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ainshams University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Premature infants diagnosed with aggressive posterior retinopathy of prematurity (AP-ROP) according to the International Classification of Retinopathy of Prematurity.
• Gestational age ≤34 weeks or birth weight ≤2000 g.
• Infants with gestational age >34 weeks or birth weight >2000 g were eligible if they had additional systemic risk factors, including respiratory distress syndrome, patent ductus arteriosus, sepsis, necrotizing enterocolitis, need for mechanical ventilation, or blood transfusion.
• Infants whose parents or legal guardians provided written informed consent for treatment and follow-up.

Exclusion Criteria:

• Previous treatment for retinopathy of prematurity with intravitreal anti-VEGF therapy, laser photocoagulation, cryotherapy, or vitreoretinal surgery.
• Presence of retinal disease other than retinopathy of prematurity.
• Major congenital ocular anomalies that could interfere with retinal assessment or treatment response.
• Known genetic syndromes or systemic conditions judged by the investigators to significantly affect retinal vascular development or study follow-up.
• Media opacity or other ocular condition preventing adequate fundus examination or retinal imaging.
• Inability to complete the planned follow-up schedule.
• Refusal or withdrawal of consent by parents or legal guardians.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intra-vitreal injection of Ranibizumab; Premature infants diagnosed with aggressive posterior retinopathy of prematurity (AP-ROP) received intravitreal ranibizumab (0.25 mg/0.025 mL) as the primary treatment. Eyes were followed with serial ophthalmic examinations and retinal imaging to evaluate disease regression, reactivation, retinal vascularization, anatomical outcomes, and treatment-related complications. Eyes demonstrating disease reactivation received repeat intravitreal ranibizumab according to the study protocol.

Drug: Intravitreal Ranibizumab injection; Intravitreal ranibizumab (0.25 mg in 0.025 mL) was administered under sterile conditions using a 30-gauge needle through the pars plicata, 1.5 mm posterior to the corneal limbus. Repeat injections were performed in eyes with disease reactivation according to the study protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease regression following intravitreal ranibizumab	Proportion of eyes demonstrating regression of aggressive posterior retinopathy of prematurity (AP-ROP), defined by disease resolution or involution in the form of resolution of plus disease, reduction in vascular tortuosity and dilation, regression of extraretinal neovascularization, and continued peripheral retinal vascularization.	1 week after the initial intravitreal ranibizumab injection
Disease regression following intravitreal ranibizumab	Proportion of eyes demonstrating regression of aggressive posterior retinopathy of prematurity (AP-ROP), defined by disease involution & resolution in the form of resolution of plus disease, reduction in vascular tortuosity and dilation, regression of extraretinal neovascularization, and continued peripheral retinal vascularization.	1 week after the initial intravitreal ranibizumab injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Reactivation	Incidence of AP-ROP reactivation requiring retreatment following initial disease regression	From the initial injection until completion of follow-up (up to 72 weeks postmenstrual age).
Time to first reactivation	Postmenstrual age (PMA) at the first episode of disease reactivation requiring retreatment.	Up to 72 weeks postmenstrual age.
Number of intravitreal ranibizumab injections	Number of intravitreal ranibizumab injections required per eye during the study period.	Up to 72 weeks postmenstrual age.
Complete retinal Vascularization	Proportion of eyes achieving complete peripheral retinal vascularization.	up to 72 weeks postmenstrual age
Treatment-related complications	Incidence of ocular or systemic complications associated with intravitreal ranibizumab treatment.	From treatment until completion of follow-up (up to 72 weeks postmenstrual age).

Collaborators and Investigators

• Sponsor: Ain Shams University
• Investigators: Principal Investigator: Ahmed Mansour, MD, PhD, Ainshams University

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2021
• Primary Completion (Actual): September 1, 2024
• Study Completion (Actual): February 1, 2025

Study Registration Dates

• First Submitted: July 18, 2026
• First Submitted That Met QC Criteria: July 18, 2026
• First Posted (Actual): July 23, 2026

Study Record Updates

• Last Update Posted (Actual): July 23, 2026
• Last Update Submitted That Met QC Criteria: July 18, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Ranibizumab; ROP; Reactivation; APROP; Aggressive posterior retinopathy of prematurity; Intra-vitreal Injection
• Additional Relevant MeSH Terms: Infant, Premature, Diseases; Infant, Newborn, Diseases; Eye Diseases; Retinal Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Retinopathy of Prematurity
• Other Study ID Numbers: 163/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data underlying the results reported in this study, including demographic characteristics, baseline clinical variables, treatment data, follow-up assessments, and outcome measures, will be made available.
• IPD Sharing Time Frame: Beginning 6 months following publication and ending 5 years after publication.
• IPD Sharing Access Criteria: De-identified individual participant data will be available to qualified researchers upon reasonable request. Requests should include a methodologically sound research proposal and will be reviewed by the study investigators. Data will be provided after approval of the proposal and execution of a data sharing agreement, where applicable.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes