Intravitreal Alfibercept for Center Involved DME Previously Managed With Intravitreal Ranibizumab

This is a phase 4 prospective, nonrandomized, open label, interventional clinical trial to
determine the efficacy of intravitreal aflibercept (IAI) administered in a treat and extend
fashion in eyes that have persistent centered involved diabetic macular edema despite at
least 4 intravitreal injections of ranibizumab 0.3mg over 24 weeks prior to enrollment.
Patients will receive intravitreal injections of aflibercept (2mg/0.05cc) at baseline and
monthly until an eye has reached stability defined as: < 10% change in the Spectral Domain
Optical Coherence Tomography (SD OCT) central retinal thickness (CRT) reading from the
previous 2 visits (can include baseline) and less than a 5 letter decrease in Best Corrected
Visual Acuity (BCVA) from best BCVA from prior visits. Once an eye has reached stability
criteria, a treat and extend protocol will be used and treatment will be rendered on every
visit. The duration between treatments will be extended by 2 weeks from the last visit if SD
OCT extension criteria are met: < 10% change in CRT over 2 consecutive visits and < 5 letter
decrease in BCVA from baseline

If at any return visit subretinal and/or intraretinal fluid recurs that causes the CRT to
increase by > 10 % from its lowest level in the previous 2 consecutive visits, or CRT
increases by < 10% due to subretinal and/or intraretinal fluid but is associated with a
decrease of BCVA of > 5 letters from baseline then the eye will receive IAI and the treatment
interval will be decreased by 1 week. If the eye has not improved or worsened for at least 2
consecutive visits and the SD OCT central subfield thickness is ≥ 300 microns or visual
acuity is worse than 20/20, the following will be done:

Prior to the 24-week visit, an injection will be given. At and after the 24-week visit, an
injection will be given and modified grid laser can be given at the discretion of the
investigator within 7 days of IAI based on rescue criteria

Inclusion Criteria:

- Age ≥18 years with type 1 or type 2 diabetes

- Best Corrected Visual Acuity (by ETDRS) letter score in study eye ≤ 85 and ≥24
(approximate Snellen equivalent 20/20 to 20/320)

- Central retinal thickness on SD OCT at baseline visit of > 300 microns using
Heidelberg Spectralis with definite evidence of intraretinal or subretinal fluid due
to diabetic retinopathy in the CSF.

- Patients must have received at least four intravitreal ranibizumab 0.3 mg injections
within 24 weeks prior to screening and failed to have had complete resolution of
intraretinal or subretinal fluid on SD OCT and a CRT > 300 microns using Heidelberg
Spectralis

Exclusion Criteria:

- Laser photocoagulation (panretinal or macular) in the study within 90 days of baseline

- Active high risk proliferative diabetic retinopathy (PDR)

- History of intravitreal corticosteroids within 4 months of baseline

- History of intravitreal bevacizumab within 24 weeks of baseline

- History of idiopathic or autoimmune uveitis in the study eye

- Cataract surgery in the study eye within 90 days of baseline

- Any intraocular surgery within 90 days of baseline

- Vitreomacular traction or epiretinal membrane in the study eye that is thought to
affect vision

- Evidence of active infection in either eye

- Uncontrolled glaucoma in the study eye defined as a pressure of > 25 mmHg on maximal
medical therapy.