Peripheral and Macular Retinal Vascular Perfusion and Leakage in DME and RVO

Diabetic macular edema (DME) and macular edema secondary to retinal venous occlusive diseases
are the most common cause of vision loss from a retinal vascular disease. Recently VEGF
inhibitors (bevacizumab, aflibercept, and ranibizumab) have been described as new first-line
therapies for these conditions. Aflibercept is the most recently approved VEGF inhibitor for
the management of these conditions. Clinical trials have shown that treatment with
aflibercept improves visual acuity and reduces macular edema in a large percentage of
patients.

This study will examine the changes that occur with intravitreal aflibercept to perfusion and
leakage in treatment naive eyes over the course of 1 year.

Inclusion Criteria

A subject must meet the following criteria to be eligible for inclusion in the study:

1. Signed Informed Consent.

2. Men and women ≥ 18 years of age.

3. Foveal-involving retinal edema secondary to DME or RVO based on investigator review of
SDOCT.

4. E-ETDRS best-corrected visual acuity of: 20/25 to 20/400 in the study eye or Hand
Motion (HM) in the study eye.

5. Willing, committed, and able to return for ALL clinic visits and complete all study
related procedures.

6. Able to read, (or, if unable to read due to visual impairment, be read to verbatim by
the person administering the informed consent or a family member) understand and
willing to sign the informed consent form.

Exclusion Criteria

A subject who meets any of the following criteria will be excluded from the study:

1. Any prior or concomitant therapy with another investigational agent to treat DME or
RVO in the study eye.

2. Prior panretinal photocoagulation in the study eye.

3. Prior intravitreal anti-VEGF therapy in the study eye.

4. Prior focal/grid laser photocoagulation in the study eye.

5. Prior history of intravitreal steroid therapy in the study eye.

6. Any history of allergy to fluorescein sodium or other reason that the patient is
unable to undergo fluorescein angiography (e.g., inability to get vascular access,
unable to tolerate procedure)

7. Prior systemic anti-VEGF therapy, investigational or FDA-approved, is only allowed up
to 3 months prior to first dose, and will not be allowed during the study.

8. Significant vitreous hemorrhage obscuring view to the macula or the retinal periphery
as determined by the investigator on clinical exam and ultra-widefield angiography.

9. Presence of other causes of macular edema, including myopic degeneration, ocular
histoplasmosis syndrome, angioid streaks, choroidal rupture, choroidal
neovascularization, neovascular age-related macular degeneration or multifocal
choroiditis in the study eye. Epiretinal membranes are allowed.

10. Presence of macula-threatening traction retinal detachment.

11. Prior vitrectomy in the study eye.

12. History of retinal detachment or treatment or surgery for retinal detachment in the
study eye.

13. Any history of macular hole of stage 2 and above in the study eye.

14. Any intraocular or periocular surgery within 3 months of Day 1 on the study eye,
except lid surgery, which may not have taken place within 1 month of day 1, as long as
it's unlikely to interfere with the injection.

15. Prior trabeculectomy or other filtration surgery in the study eye.

16. Uncontrolled glaucoma at baseline evaluation (defined as intraocular pressure ≥25 mmHg
despite treatment with anti-glaucoma medication) in the study eye.

17. Active intraocular inflammation in either eye.

18. Active ocular or periocular infection in either eye.

19. Any ocular or periocular infection within the last 2 weeks prior to Screening in
either eye.

20. Any history of uveitis in either eye.

21. Active scleritis or episcleritis in either eye.

22. Presence or history of scleromalacia in either eye.

23. Aphakia in the study eye.

24. Previous therapeutic radiation in the region of the study eye.

25. History of full-thickness penetrating keratoplasty in the study eye. Partial thickness
corneal transplants including DSAEK and DMEK are allowed.

26. Significant media opacities, including cataract, in the study eye which might
interfere with visual acuity, assessment of safety, or fundus photography.

27. Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the
opinion of the investigator, could require either medical or surgical intervention
during the 52 week study period.

28. Any concurrent ocular condition in the study eye which, in the opinion of the
investigator, could either increase the risk to the subject beyond what is to be
expected from standard procedures of intraocular injection, or which otherwise may
interfere with the injection procedure or with evaluation of efficacy or safety.

29. Participation as a subject in any clinical study within the 12 weeks prior to Day 1.

30. Any systemic therapy with an investigational agent in the past 3 months prior to Day
1.

31. Any history of allergy to povidone iodine.

32. Pregnant or breast-feeding women

33. 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
plus contraceptive sponge, foam, or jelly)

- 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.