NEWTON: Aflibercept Injection for Previously Treated Macular Edema Associated With Central Retinal Vein Occlusions

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 aflibercept injection for macular edema following CRVO. All patients will
receive IAI 2 mg at baseline and Week 4. If the pre-defined 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 two weeks. If the extension criteria are not met on a
follow-up visit, the treatment interval will be continued 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 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 IAI is rendered at every
visit.

Inclusion Criteria:

- Patients aged 18 and above with documented history of center-involved macular edema
secondary to CRVO.

- Patients must have received treatment for at least 6 months before baseline, with 3
initial loading doses, and evidence of recurrence of edema when extended beyond 4
weeks.

- Protocol refracted ETDRS BCVA of 20/25 to 20/320 (73-24 letters).

- Willing and able to comply with clinic visits and study-related procedures.

- Provide signed informed consent.

Exclusion Criteria:

- Prior panretinal or macular laser photocoagulation

- Previous use of intraocular corticosteroids or use of periocular corticosteroids
within the 3 months prior to 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 1 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 intraocular pressure equal or
greater than 30mmHg despite treatment with anti-glaucoma medication)

- Concurrent eye disease in the study eye that could compromise visual acuity (e.g.
advanced glaucoma, age-related macular degeneration, etc)

- Any concurrent intraocular condition in the study eye (e.g. glaucoma) that, in the
opinion of the investigator, could either require medical or surgical intervention
during the 52 weeks 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 (adequate contraceptive measures
include stable use of oral contraceptives or other prescription pharmaceutical
contraceptives for 2 or more menstrual cycles prior to screening; intrauterine device
[IUD]; bilateral tubal ligation; vasectomy; condom plus, contraceptive sponge, foam
or jelly, or diaphragm) *Contraception is not required for men with documented
vasectomy. **Postmenopausal women must be amenorrheic for at least 12 months in order
not to be considered of child bearing potential. Pregnancy testing and contraception
are not required for women with documented hysterectomy or tubal ligation.