Please select the eligibility criteria that correspond to the clinical trial below.
Title: Research Study in Patients With Persistent Macular Edema Due to Diabetic Retinopathy, Retinal Vein Occlusion, Uveitis, or Irvine-Gass Syndrome
Brief Summary: The purpose of this clinical research study is to evaluate the safety and effectiveness of an investigational medication to treat macular edema that persists despite current treatment methods. Participants will be evaluated for improvement in vision and side effects.

Macular edema is a condition that affects the back of the eye (retina). It frequently occurs in people who have a history of diabetes, and is also associated with high blood pressure, uveitis, and previous eye surgery. The main symptom of macular edema is decreased vision, generally a blurring of central vision.

There are no direct costs to participants for assessments and treatment as defined in the study protocol. All candidates must be available for required scheduled visits during the trial's 6-month follow-up period. Although the disease called age-related macular degeneration (AMD) affects the same region of the eye as macular edema, they are not the same condition and AMD is not studied in this research trial.


Options:
A: Inclusion: Persistent macular edema associated with diabetic retinopathy, uveitis, retinal vein occlusion, or Irvine-Gass syndrome, persisting at least 90 days after laser treatment or medical management by a physician.

Exclusion: Females who are pregnant or lactating, and females of childbearing potential not using adequate birth control for the duration of the study. Any intraocular procedures or laser treatment less than 90 days before enrollment.
B: General Inclusion Criteria

* Age \>= 18 years
* Diagnosis of diabetes mellitus (type 1 or type 2)
* Fellow eye (if not a study eye) meets criteria.
* Able and willing to provide informed consent. Study Eye Inclusion Criteria Subjects may have one or two study eyes. Subjects with two study eyes will be randomly assigned to receive sham injection at baseline and 4 weeks in one eye and either ranibizumab or triamcinolone in the other eye.
* Presence of severe nonproliferative or proliferative diabetic retinopathy for which investigator intends to complete panretinal photocoagulation within 49 days after randomization.
* Diabetic macular edema(DME) present on clinical exam and central subfield thickness on Optical Coherence Tomography (OCT) \>250 microns, within 8 days of randomization.
* Best corrected Electronic-Early Treatment Diabetic Retinopathy Study visual acuity letter score \>=24 (i.e., 20/320 or better), within 8 days of randomization.
* Media clarity, pupillary dilation, and subject cooperation sufficient to administer panretinal photocoagulation and obtain adequate fundus photographs and OCT.
* If prior macular photocoagulation has been performed, the investigator believes that the study eye may possibly benefit from additional focal photocoagulation.

General Exclusion Criteria

* 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 drugs.
* 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 endothelial growth factor(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 12 months of the study.

Study Eye Exclusion Criteria, Study eye only:

* Prior panretinal photocoagulation that was sufficiently extensive that the investigator does not believe that at least 1200 additional burns are needed or possible within 49 days after randomization.
* 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, preventing visual acuity loss would not improve from resolution of macular edema (e.g., foveal atrophy, pigment abnormalities, dense subfoveal hard exudates, non-retinal 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., retinal vein or artery 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 DME 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 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 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: angle-closure glaucoma is not an exclusion criterion).
* History of steroid-induced intraocular pressure elevation that required intraocular pressure-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.

Fellow Eye Criteria

* Intraocular pressure \< 25 mmHg.
* No history of open-angle glaucoma (either primary open-angle glaucoma or other cause of open-angle glaucoma; note: angle-closure glaucoma is not an exclusion criterion).
* No history of steroid-induced intraocular pressure elevation that required intraocular pressure-lowering treatment.
* No exam evidence of pseudoexfoliation.
C: 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 next 12 months;
* 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
D: 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.

Answer: A