Intravitreal Aflibercept Injection for Radiation Retinopathy Trial
Intravitreal Aflibercept Injection for Radiation Retinopathy Trial
The ARRT trial will assess the safety and efficacy of 2mg aflibercept for the treatment of
 radiation retinopathy, including maculopathy and optic neuropathy over 52 weeks.
Approximately 40 eyes will be randomized (1:1 ratio) into either Group 1 or Group 2. Slit
 lamp exam and Indirect ophthalmoscopy will be performed at every study visit, where
 retinopathy level will be assessed. SD-OCT will be performed at each visit. Fluorescein
 angiogram will be performed at screen, week 26 and week 52. All other imaging studies will be
 standard of care at the discretion of the investigator.

 This trial will compare the results of 2 groups, with different treatment intervals, to
 assess the safety of intravitreal Aflibercept injections (IAI) for the treatment of radiation
 retinopathy. Patients in each group will be followed for a total of 52 weeks.

 Group 1: 15 Patients will receive a loading dose of 3 IAI. They will receive 2 mg IAI at
 screening/baseline, week 4, week 8, and week 12. A follow-up visit will occur at week 12. If
 the extension criteria are met, the patient will be extended by 2 weeks. The patient will
 continue to be followed per the treat and extend protocol described below.

 Group 2: Patients will not receive a loading dose. They will receive 2 mg IAI at
 screening/baseline followed by a visit at week 4. At week 4, if the extension criteria are
 met, the patient will be extended by 2 weeks. The patient will continue to be followed per
 the treat and extend protocol described below.

 Treat & Extend Protocol Patients can be extended as long as they meet the following criteria
 -

 -  Absence of retinal fluid (resolution of intraretinal and subretinal fluid on SD-OCT;
 Small intraretinal cysts that do not distort foveal contour on SD-OCT are acceptable and
 can be considered "dry".) AND

 -  Less than 5 ETDRS letter loss from previous visit due to new or persistent retinal
 edema.

 IAI will be rendered at every visit (treatment at the week 26 mandatory visit will be
 administered based on the treat and extend status), no earlier than 4 days before the target
 date and no later than 4 days after the target date. Each extension will be 2 weeks in
 duration beyond the initial 4-week interval. If the extension criteria are not met on a
 follow-up visit, the treatment interval will be reduced by 2 weeks. Follow up interval will
 continue to be reduced by 2 weeks until the extension criteria are met or a 4-week interval
 is reached.

 All patients will have a mandatory study visit at Week 52 (final study visit). No study
 treatment will be administered after week 50 or at a study termination visit. If a patient
 receives treatment after week 48, they will return 4 weeks after the last clinic visit for
 the final study visit (instead of at week 52).
Inclusion Criteria:

 1. Age > 18 years of age

 2. Clinically identifiable radiation retinopathy with evidence of fluid on SD-OCT causing
 vision loss in the study eye

 3. Undergone either ocular or orbital radiation for any primary ocular or orbital cancer
 within clinical evidence of having radiation retinopathy

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

 5. Provide signed informed consent

 Exclusion Criteria:

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

 1. Metastatic cancer or any active primary cancer, at time of enrollment

 2. Prior treatment with anti VEGF in the study within 60 days of screen in the study eye

 3. Prior intravitreal or subconjunctival treatment with cortical steroids within 90 days
 of screen in the study eye

 4. Macular ischemia (defined as greater than 5 disc areas), as assessed by the
 investigator

 5. Media opacity obscuring a view of the fundus or any other reason for vision loss other
 than radiation retinopathy.

 6. Evidence of infectious ocular infection, in the study eye, at time of screening

 7. Pregnant or breast-feeding women

 8. Sexually active men* or women of childbearing potential** who are unwilling to
 practice adequate contraception start of the first treatment, during the study, and
 for at least 3 months after the last dose. 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; bilateral
 tubal ligation; vasectomy; condom plus contraceptive sponge, foam, or jelly, or
 diaphragm plus contraceptive sponge, foam, or jelly.

 -  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
 childbearing potential. Pregnancy testing and contraception are not required for
 women with documented hysterectomy or tubal ligation.