NEWTON: Aflibercept injection for previously treated macular edema associated with central retinal vein occlusions

Institution: Northern California Retina Vitreous Associates

Author/principal investigator: Rahul Khurana, MD

Abstract/statement of the trial’s goals

This prospective, open-label, single-center, nonrandomized, investigator-sponsored clinical study seeks to investigate the visual outcomes of a treat-and-extend dosing regimen of intravitreal Eylea (aflibercept, Regeneron) injection for macular edema following central retinal vein occlusion. All patients will receive intravitreal aflibercept injection 2 mg at baseline and week 4. If the predefined extension criteria are met at the 4-week visit, and at any follow-up visit, the patient will receive a mandated treatment, and the next visit will be extended by 2 weeks. If the extension criteria are not met on a follow-up visit, the treatment interval will continue to be reduced by 1 week. If criteria are still not met despite treatment at the reduced interval, treatment will be administered as usual and the follow-up interval will continue to be reduced by 1 week until the criteria are met or a 4-week interval is reached. Treatment of intravitreal aflibercept injection is rendered at every visit.

ClinicalTrials.gov identifier: NCT01870427

Study population: 20

Inclusion criteria

Patients aged 18 years and older with documented history of center-involved macular edema secondary to CRVO.
Patients must have received treatment for at least 6 months before baseline, with three initial loading doses and evidence of recurrence of edema when extended beyond 4 weeks.
Protocol refracted ETDRS best corrected visual acuity of 20/25 to 20/320 (73 to 24 letters).

Exclusion criteria

Prior panretinal or macular laser photocoagulation.
Previous use of intraocular corticosteroids or use of periocular corticosteroids within the 3 months before day 1.
Prior treatment with systemic anti-VEGF agents.
Presence of iris neovascularization.
Vitreous hemorrhage in the study eye.
Traction retinal detachment or preretinal fibrosis involving the macula.
Diabetic macular edema or diabetic retinopathy, defined as eyes of diabetic patients with more than one microaneurysm outside the area of the vein occlusion.
Infectious blepharitis, keratitis, scleritis or conjunctivitis.
Active intraocular inflammation (grade trace or above) in the study eye or history of idiopathic or autoimmune-associated uveitis in either eye.
Uncontrolled glaucoma in the study eye (defined as IOP equal to or greater than 30 mm Hg despite treatment with antiglaucoma medication).
Concurrent eye disease in the study eye that could compromise visual acuity (eg, advanced glaucoma, age-related macular degeneration).
Any concurrent intraocular condition in the study eye (eg, glaucoma) that, in the opinion of the investigator, could either require medical or surgical intervention during the 52-week study period to prevent or treat visual loss that might result from that condition.
Pregnant or breast-feeding women.
Sexually active men or women of childbearing potential who are unwilling to practice adequate contraception during the study.

Enrollment status: Currently recruiting participants

A note from the institution regarding the value of this trial

Anti-VEGF therapy is effective for the treatment of macular edema associated with central retinal vein occlusions (CRVO). The original CRUISE study with ranibizumab (Lucentis, Genentech) showed excellent results at the 6-month endpoint. However, more injections were needed afterward to maintain those visual outcomes. In practice, the durability of ranibizumab is limited and interval between treatments is short.

We propose examining patients with central retinal vein occlusions who are receiving ranibizumab or bevacizumab and developing recurrences of macular edema after treatment when their follow-up is extended beyond 4 weeks. These patients will be switched to aflibercept (Eylea, Regeneron) to see if their treatment interval can be extended using a “treat and extend” strategy. The majority of retina specialists utilize a “treat and extend” strategy, and we would like to determine if aflibercept may extend the treatment interval for patients previously on ranibizumab and/or bevacizumab.