Objective: To determine the association between baseline aqueous cytokine levels and treatment intervals for patients under a variable dosing regimen with intravitreal aflibercept in patients with neovascular age-related macular degeneration (nAMD), macular edema secondary to retinal vein occlusion (RVO) and diabetic macular edema (DME).

Methods: A prospective, single-centre study will be performed containing 3 sub-studies according to each study population: nAMD, macular edema secondary to RVO and DME. Inclusion criteria are: patients followed at St. Michael's Hospital with the diagnosis of nAMD, macular edema secondary to RVO or DME. Patients will be excluded if visual acuity is worse than counting fingers, with macular pathologies causing any structural changes to the retina, have received anti-VEGF injections or photocoagulation therapy 6 months prior to study, intraocular surgery 3 months prior to study, any history of vitreoretinal surgery or ocular inflammation in the study eye, use of systemic or topical anti-inflammatory or steroids, patients on dialysis for renal failure, allergy to the study drug or fluorescein, <18 years old, women who are pregnant. All patients will be treated with aflibercept intravitreal injections on a variable dosing regimen: Patients with DME will be examined monthly and receive mandatory injection for the first three months (baseline, weeks 4 and 8). Afterwards, they will continue to be seen monthly and the need for new injections will be decided upon the clinical findings at each visit. An anterior chamber (AC) tap will be done if an injection is required at the visit. Patients with nAMD and RVO will be examined monthly and receive mandatory injection for the first three months. From weeks 12 until 72 (month 18), the visits will be scheduled at increasing 2-weeks intervals based on the stability of the ocular condition and response to treatment. At each visit, an injection and AC tap will be performed. The maximum interval in between injections is 12 weeks. If the disease becomes unstable, the interval in between injections is shortened and, once it stabilizes, the treatment frequency is extended again. In all patients, baseline aqueous humour specimens will be obtained prior to the first aflibercept intravitreal injection and follow-up samples will be taken immediately prior to subsequent injections based on the treatment regimens for cytokine analysis in the end of the follow-up.

Inclusion Criteria:

• Diagnosis of active choroidal neovascularization secondary to AMD in the study eye
• Diagnosis of macular edema secondary to RVO: central macular thickness >310μm due to intraretinal or subretinal edema in the study eye as measured on OCT
• Diagnosis of DME with central macular thickness >310μm in the study eye as measured on OCT in patients with diabetes mellitus types 1 or 2

Exclusion Criteria:

• • Previous intravitreal drug injections in either eye within 6 months prior to study enrollment

  • Visual acuity worse than counting fingers
  • Patients with other macular pathologies causing structural changes to the retina
  • Patients with large submacular hemorrhages or extensive fibrosis occupying the majority (>50%) of the lesion
  • Intraocular surgery in the study eye 3 months prior to study enrollment
  • Previous vitreoretinal surgery in the study eye
  • Previous photodynamic or macular photocoagulation therapy within the past 6 months in the study eye in patients with AMD
  • Previous photocoagulation therapy within 6 months in the study eye or anticipated need for during the course of the study in patients with RVO
  • Presence of active proliferative diabetic retinopathy or patients who have had pan-retinal photocoagulation within 6 months or patients where the need to pan-retinal photocoagulation is anticipated during the course of the study in patients with DME
  • History of intraocular inflammation in the study eye
  • Patients on systemic or topical anti-inflammatory or steroids medications
  • Patients receiving dialysis for renal failure
  • Known allergy to the study drug or fluorescein
  • Patients who are pregnant
  • Unwilling or unable to follow or comply with all study related procedures or to sign consent form