Peripheral and Macular Retinal Vascular Perfusion and Leakage in DME and RVO
Condition: Retinal Vein Occlusion; Diabetic Macular Edema; Branch Retinal Vein Occlusion; Central Retinal Vein Occlusion
MeSH terms: Macular Edema; Retinal Vein Occlusion; Edema
Intervention: Aflibercept
Intervention description: Intravitreal aflibercept will be given q4 wks for 6 treatments and then q 8 weeks through month 12.
Intervention MeSH terms: Aflibercept
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 31.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: macular edema; rvo; diabetic macular edema

Summary:

      This interventional study will evaluate the retinal vascular dynamics associated with
      Intravitreal Aflibercept Injection (IAI) therapy in eyes with diabetic macular edema (DME) or
      macular edema secondary to retinal vein occlusion (RVO). Ultra-widefield fluorescein
      angiography and optical coherence tomography (OCT) angiography will be performed at multiple
      timepoints to assess the changes in retinal vascular leakage, ischemia, and vascular
      abnormalities throughout the study duration and compare these alterations to baseline.
    

Eligibility criteria:

        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 Descemet stripping automated endothelial keratoplasty
             and Descemet membrane endothelial keratoplasty 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.