Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2 Evaluation of Anti-VEGF Therapy for Diabetic Macular Edema: Bevacizumab (Avastin)
Brief Summary: This study will provide preliminary data on the dose and dose interval related effects of intravitreally administered Avastin on retinal thickness and visual acuity in subjects with Diabetic Macular Edema (DME) to aid in planning a phase 3 trial.

In addition, this study will provide preliminary data on the safety of intravitreally administered Avastin in subjects with DME.


Options:
A: Key Inclusion Criteria:

* 18 years of age or older with diabetic macular edema;
* Decrease in visual acuity in at least one eye as a result of macular edema (20/50 or worse);
* Visual acuity in other eye no worse than 20/200

Key Exclusion Criteria:

* Known anticipated need for ocular surgery within first 12 months of study;
* History of glaucoma or current high eye pressure requiring more than 1 medication;
* Uncontrolled systemic disease;
* Known steroid-responder;
* Use of systemic steroids
* Use of Warfarin/Heparin
B: Inclusion Criteria:

Participation in the study will be offered to all patients at the conclusion of the TDMO study. Currently we are still following 64 of the 69 (93%) eyes that were initially entered into the study that had reduced vision from diabetic macular oedema at baseline.

Exclusion Criteria:

* Uncontrolled glaucoma
* Loss of vision due to other causes (e.g. age related macular degeneration, myopic macular degeneration)
* known allergies to triamcinolone acetate, patient is already receiving systemic steroid treatment, intercurrent severe disease such as septicemia, any condition which would affect follow-up or photographic documentation (e.g. geographical, psycho-social, media opacities)
C: SUBJECT-LEVEL INCLUSION CRITERIA

To be eligible, the following inclusion criteria (1-3) must be met:

1. Age \>= 18 years
2. Diagnosis of diabetes mellitus (type 1 or type 2)
3. Able and willing to provide informed consent.

   EXCLUSION

   A subject is not eligible if any of the following exclusion criteria (4-13) are present:
4. Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
5. A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
6. Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
7. Known allergy to any component of the study drug.
8. Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110).
9. Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
10. Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 6 months prior to randomization.
11. Systemic anti-VEGF or pro-VEGF treatment within 3 months prior to randomization.
12. For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 6 months.
13. Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 6 months of the study.

STUDY EYE CRITERIA

The subject must have one eye meeting all of the inclusion criteria (a-e) and none of the exclusion criteria (f-r) listed below.

Subjects can have only one study eye. If both eyes are eligible, the study eye will be selected by the investigator and subject.

The eligibility criteria for a study eye are as follows:

INCLUSION

1. Best corrected E-ETDRS visual acuity letter score of \>= 24 (i.e., 20/320 or better) and \<= 78 (i.e., 20/32 or worse) within 8 days of randomization.
2. On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
3. OCT central subfield \>=275 microns within 8 days of randomization.
4. Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
5. If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

   EXCLUSION

   The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):
6. Macular edema is considered to be due to a cause other than diabetic macular edema.
7. An ocular condition is present such that, in the opinion of the investigator, visual acuity would not improve from resolution of macular edema (e.g., foveal atrophy, pigmentary changes, dense subfoveal hard exudates, nonretinal condition).
8. An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, Irvine-Gass Syndrome, etc.).
9. Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
10. History of treatment for DME at any time in the past 3 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).
11. History of panretinal scatter photocoagulation (PRP) within 4 months prior to randomization.
12. Anticipated need for PRP in the 6 months following randomization.
13. History of prior pars plana vitrectomy.
14. History of major ocular surgery (including cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 6 months or anticipated within the next 6 months following randomization.
15. History of YAG capsulotomy performed within 2 months prior to randomization.
16. Aphakia.
17. Uncontrolled glaucoma (in investigator's judgment).
18. Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

FELLOW EYE CRITERIA

The fellow eye must meet the following criteria:

1. Best corrected E-ETDRS visual acuity letter score \>= 19 (i.e., 20/400 or better).
2. No anti-VEGF treatment within the past 3 months and no expectation of such treatment in next 3 months.
D: General Inclusion Criteria

To be eligible, the following inclusion criteria (1-5) must be met:

* Age \>= 18 years
* Diagnosis of diabetes mellitus (type 1 or type 2)
* At least one eye meets the study eye criteria
* Fellow eye (if not a study eye) meets criteria
* Able and willing to provide informed consent

General Exclusion Criteria

A subject is not eligible if any of the following exclusion criteria are present:

* Significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant.
* A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
* Participation in an investigational trial within 30 days of randomization that involved treatment with any drug that has not received regulatory approval at the time of study entry.
* Known allergy to any component of the study drug.
* Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110).
* Major surgery within 28 days prior to randomization or major surgery planned during the next 6 months.
* Myocardial infarction, other cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
* Systemic anti-vascular growth factor (anti-VEGF) or pro-VEGF treatment within 4 months prior to randomization.
* For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 12 months.
* Subject is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the first 12 months of the study.

Study Eye Inclusion Criteria

The subject must have one eye meeting all of the inclusion criteria and none of the exclusion criteria listed below. A subject may have two study eyes only if both are eligible at the time of randomization.

* Best corrected electronic Early Treatment Diabetic Retinopathy (E-ETDRS) visual acuity letter score \<= 78 (i.e., 20/32 or worse) and \>= 24 (i.e., 20/320 or better) within 8 days of randomization.
* On clinical exam, definite retinal thickening due to diabetic macular edema involving the center of the macula.
* Ocular coherence tomography (OCT) central subfield \>=250 microns within 8 days of randomization.
* Media clarity, pupillary dilation, and subject cooperation sufficient for adequate fundus photographs.
* If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional photocoagulation.

Study Eye Exclusion Criteria

The following exclusions apply to the study eye only (i.e., they may be present for the nonstudy eye):

* Macular edema is considered to be due to a cause other than diabetic macular edema.
* An ocular condition is present such that, in the opinion of the investigator, visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, nonretinal condition).
* An ocular condition is present (other than diabetes) that, in the opinion of the investigator, might affect macular edema or alter visual acuity during the course of the study (e.g., vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
* Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by 3 lines or more (i.e., cataract would be reducing acuity to 20/40 or worse if eye was otherwise normal).
* History of treatment for diabetic macular edema at any time in the past 4 months (such as focal/grid macular photocoagulation, intravitreal or peribulbar corticosteroids, anti-VEGF drugs, or any other treatment).
* History of panretinal (scatter) photocoagulation (PRP) within 4 months prior to randomization.
* Anticipated need for PRP in the 6 months following randomization.
* History of major ocular surgery (including vitrectomy, cataract extraction, scleral buckle, any intraocular surgery, etc.) within prior 4 months or anticipated within the next 6 months following randomization.
* History of yttrium aluminum garnet (YAG) capsulotomy performed within 2 months prior to randomization.
* Aphakia.
* Intraocular pressure \>= 25 mmHg.
* History of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: history of angle-closure glaucoma is not an exclusion criterion).
* History of steroid-induced intraocular pressure (IOP) elevation that required IOP-lowering treatment.
* History of prior herpetic ocular infection.
* Exam evidence of ocular toxoplasmosis.
* Exam evidence of pseudoexfoliation.
* Exam evidence of external ocular infection, including conjunctivitis, chalazion, or significant blepharitis.

Answer: C