Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Double-masked, Multicenter, Randomized, Sham Injection-controlled Study of the Efficacy and Safety of Ranibizumab Injection in Subjects With Clinically Significant Macular Edema With Center Involvement Secondary to Diabetes Mellitus
Brief Summary: This study is a Phase III, double-masked, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection in patients with clinically significant macular edema with center involvement (CSME-CI) secondary to diabetes mellitus (Type 1 or 2). This study is identical in design to study NCT00473330 (Protocol ID FVF4170g).

The open-label extension phase of the study was stopped after receiving FDA approval of the study drug (ranibizumab) for diabetic macular edema.


Options:
A: Inclusion Criteria:

* Primary eye diagnosis (better seeing Eye) macular disease
* Best-corrected visual acuity (better seeing eye) 20/50-20/200

Exclusion Criteria:

* Does not have a telephone
* Does not speak English
* Has received interdisciplinary low vision services
* English literacy less that 5th grade reading level
* Failed TICS
* Unable or unwilling to attend required clinic visits
* Severe hearing impairment preventing administration of telephone questionnaires
* Planned cataract extraction in next 4 months
* Visual fields contracted to diameter of 20 degrees in better-seeing eye
* Vitreous hemorrhage or serous hemorrhagic detachment of macula
* CNVM treated with fewer than 3 anti-VEGF injections
* Diabetic macular edema (DME) treated with focal/grid laser within the last two months
* DME treated with intravitreal injections of anti-VEGF or intravitreal triamcinolone acetonide (IVTA) within the last two months
* Cystoid macular edema (CME) treated with topical (non-steroidal anti-inflammatory drugs) NSAIDS, topical steroids or IVTA within the last three months
B: Inclusion Criteria:

* Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
* Age ≥ 18 years.
* Diabetes mellitus (Type 1 or 2) .
* Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea with central macular thickness ≥ 275 µm in the center subfield as assessed on optical coherence tomography (OCT).
* Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320 approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing distance of 4 meters.
* Decrease in vision determined to be primarily the result of DME and not to other causes.
* For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study.
* Ability (in the opinion of the investigator) and willingness to return for all scheduled visits and assessments.

Exclusion Criteria:

* History of vitreoretinal surgery in the study eye.
* Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of screening.
* Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone acetonide \[TA\]) within 3 months of screening.
* Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first day of treatment) visit.
* Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR.
* Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in the study eye.

Concurrent Ocular Conditions

* Vitreomacular traction or epiretinal membrane in the study eye.
* Ocular inflammation (including trace or above) in the study eye.
* History of idiopathic or autoimmune uveitis in either eye.
* Structural damage to the center of the macula in the study eye that is likely to preclude improvement in VA following the resolution of macular edema, including atrophy of the retinal pigment epithelium (RPE), subretinal fibrosis, or organized hard-exudate plaque.
* Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) of any cause (eg, age-related macular degeneration (AMD), ocular histoplasmosis, or pathologic myopia).
* Concurrent disease in the study eye that would compromise visual acuity or require medical or surgical intervention during the study period.
* Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser capsulotomy within the past 2 months, or any other intraocular surgery within the 90 days preceding Day 0.
* Aphakia or absence of the posterior capsule in the study eye.
* Uncontrolled glaucoma or previous filtration surgery in the study eye.
* Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
* Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection.
* Uncontrolled blood pressure.
* History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
* Uncontrolled diabetes mellitus.
* Renal failure requiring dialysis or renal transplant.
* Participation in an investigational trial within 30 days prior to screening that involved treatment with any drug (excluding vitamins and minerals) or device.
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk from treatment complications.
* Pregnancy or lactation.
* History of allergy to fluorescein.
* History of allergy to ranibizumab injection or related molecule.
C: Inclusion Criteria:

* Willingness to provide written informed consent and, at U.S. sites, Health Insurance Portability and Accountability Act (HIPAA) authorization, and in other countries, as applicable according to national laws.
* Age ≥ 18 years.
* Diabetes mellitus (Type 1 or 2) .
* Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea with central macular thickness ≥ 275 µm in the center subfield as assessed on optical coherence tomography (OCT).
* Best corrected visual acuity (BCVA) score in the study eye of 20/40 to 20/320 approximate Snellen equivalent using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol at an initial testing distance of 4 meters.
* Decrease in vision determined to be primarily the result of DME and not to other causes.
* For sexually active women of childbearing potential, use of an appropriate form of contraception (or abstinence) for the duration of the study.
* Ability (in the opinion of the investigator) and willingness to return for all scheduled visits and assessments.

Exclusion Criteria:

* History of vitreoretinal surgery in the study eye.
* Panretinal photocoagulation (PRP) or macular laser photocoagulation in the study eye within 3 months of screening.
* Previous use of intraocular corticosteroids in the study eye (eg, triamcinolone acetonide \[TA\]) within 3 months of screening.
* Previous treatment with anti-angiogenic drugs in either eye (pegaptanib sodium, anecortave acetate, bevacizumab, ranibizumab, etc) within 3 months of the Day 0 (first day of treatment) visit.
* Proliferative diabetic retinopathy (PDR) in the study eye, with the exception of inactive, regressed PDR.
* Iris neovascularization, vitreous hemorrhage, traction retinal detachment, or preretinal fibrosis involving the macula in the study eye.

Concurrent Ocular Conditions

* Vitreomacular traction or epiretinal membrane in the study eye.
* Ocular inflammation (including trace or above) in the study eye.
* History of idiopathic or autoimmune uveitis in either eye.
* Structural damage to the center of the macula in the study eye that is likely to preclude improvement in VA following the resolution of macular edema, including atrophy of the retinal pigment epithelium (RPE), subretinal fibrosis, or organized hard-exudate plaque.
* Ocular disorders in the study eye that may confound interpretation of study results, including retinal vascular occlusion, retinal detachment, macular hole, or choroidal neovascularization (CNV) of any cause (eg, age-related macular degeneration (AMD), ocular histoplasmosis, or pathologic myopia).
* Concurrent disease in the study eye that would compromise visual acuity or require medical or surgical intervention during the study period.
* Cataract surgery in the study eye within 3 months, yttrium-aluminum-garnet (YAG) laser capsulotomy within the past 2 months, or any other intraocular surgery within the 90 days preceding Day 0.
* Aphakia or absence of the posterior capsule in the study eye.
* Uncontrolled glaucoma or previous filtration surgery in the study eye.
* Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia.
* Evidence at examination of infectious blepharitis, keratitis, scleritis, or conjunctivitis in either eye or current treatment for serious systemic infection.
* Uncontrolled blood pressure.
* History of cerebral vascular accident or myocardial infarction within 3 months prior to Day 0.
* Uncontrolled diabetes mellitus.
* Renal failure requiring dialysis or renal transplant.
* Participation in an investigational trial within 30 days prior to screening that involved treatment with any drug (excluding vitamins and minerals) or device.
* History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use an investigational drug, might affect interpretation of the results of the study, or renders the subject at high risk from treatment complications.
* Pregnancy or lactation.
* History of allergy to fluorescein.
* History of allergy to ranibizumab injection or related molecule.
D: Inclusion Criteria:

1. Primary eye diagnosis (in better seeing eye) of either macular degeneration, macular dystrophy, macular hole or inflammatory disease of the macula
2. Habitual visual acuity (in better seeing eye) better than 20/500 but less than 20/100

Exclusion Criteria:

1. does not have a phone
2. does not speak English
3. has previously received low vision services as part of an inpatient blind rehabilitation program
4. has participated in a low vision program that provided low vision devices to meet reading needs with low vision therapy administered by an occupational therapist or vision rehabilitation professional since most recent significant decrease in vision
5. has English literacy less than 5th grade level
6. has habitual visual acuity in better seeing eye of equal to or better than 20/100, less than or equal to 20/500
7. fails Telephone Interview of Cognitive Status (TICS) screening (score of 30 or lower)
8. has history of stroke with aphasia
9. has other health condition that would preclude follow-up (e.g. significant malignancy or life-threatening disease)
10. is unable or unwilling to attend clinic visits required for the study
11. has severe hearing impairment that interferes with participation in telephone questionnaires
12. reports significant loss of vision since last eye exam
13. has vitreous hemorrhage, serous or hemorrhagic detachment of the macula, clinically significant macular edema or cystoid macular edema that is likely to result in further loss or improvement in vision after treatment in better seeing eye
14. plans cataract extraction in the next 6 months.

Answer: B