Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Double Masked, Active Treatment-Controlled Study of the Efficacy and Safety of rhuFab V2 (Ranibizumab) Compared With Verteporfin (Visudyne) Photodynamic Therapy in Subjects With Predominantly Classic Subfoveal Neovascular Age-Related Macular Degeneration
Brief Summary: This is a phase III, multicenter, randomized, double-masked, active treatment-controlled study of intravitreally administered ranibizumab compared with verteporfin (Visudyne) photodynamic therapy (PDT) in treating subfoveal neovascular mascular degeneration.


Options:
A: Inclusion Criteria:

* Signed informed consent
* Age \>=50 years
* Active primary or recurrent subfoveal choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) in the study eye
* Lesions with occult CNV or with some classic CNV component are permissible. However, if classic CNV (well-demarcated hyperfluorescence boundaries in the early phase of the fluorescein angiogram) is present, the area of classic CNV must be \<50% of the total lesion size.
* The total area of CNV (including both classic and occult components) encompassed within the lesion must be \>=50% of the total lesion area.
* The total lesion area must be \<=12 disc areas (DA) in size.
* Best corrected visual acuity, using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts, of 20/40 to 20/320 (Snellen equivalent) in the study eye

Exclusion Criteria:

* Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye
* Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0
* Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)
* Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye
* Previous subfoveal focal laser photocoagulation in the study eye
* Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Day 0
* History of vitrectomy surgery in the study eye
* History of submacular surgery or other surgical intervention for AMD in the study eye
* Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
* Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \>=50% of the total lesion area or \>=1 disc area in size
* Subfoveal fibrosis or atrophy in the study eye
* CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
* Retinal pigment epithelial tear involving the macula in the study eye
* Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the investigator, could either: (1) Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition, or (2) If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 24-month study period
* Active intraocular inflammation (grade trace or above) in the study eye
* Current vitreous hemorrhage in the study eye
* History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
* History of idiopathic or autoimmune-associated uveitis in either eye
* Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
* Aphakia or absence of the posterior capsule in the study eye
* Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia
* Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0
* Uncontrolled glaucoma in the study eye (defined as intraocular pressure \>= 30 mmHg despite treatment with anti-glaucoma medication)
* History of glaucoma filtering surgery in the study eye
* History of corneal transplant in the study eye
* Premenopausal women not using adequate contraception
* 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 of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications
* Current treatment for active systemic infection
* History of allergy to fluorescein, not amenable to treatment
* Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
* Inability to comply with study or follow up procedures
B: Inclusion Criteria:

* • All subjects must meet the following criteria to be eligible for study entry: Signed informed consent

  * Age greater than 50 years
  * Active primary or recurrent subfoveal lesions with CNV secondary to AMD in the study eye, as defined in Table 1
  * Lesions with occult CNV or with some classic CNV component are permissible. However, if predominantly classic CNV (well-demarcated hyperfluorescence boundaries in the early phase of the fluorescein angiogram) is present, the patient must have had prior PDT (up to 3 previous photodynamic therapy treatments).
  * The OCT features that will permit participation will include retinal thickness (macular edema) ≥300 microns, subretinal fluid ≥100 microns in thickness, or a detachment of the retinal pigment epithelium ≥100 microns in thickness
  * The total area of CNV (including both classic and occult components) encompassed within the lesion must be ≥ 50% of the total lesion area
  * The total lesion area must be \<12 disc areas (DA) in size.
  * Best corrected visual acuity, using ETDRS charts, of 20/40 to 20/400 (Snellen equivalent) in the study eye
  * Only one eye will be assessed in the study. If both eyes are eligible, the one with the better acuity will be selected for treatment and study unless, based on medical reasons, the investigator deems the other eye the more appropriate candidate for treatment and study.

Exclusion Criteria:

* • Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy in the study eye (predominantly classic CNV can however only be included if the subject had up to 3 prior PDT treatments)

  * Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0
  * Previous participation in a clinical trial (for either eye) involving anti angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)
  * Previous subfoveal focal laser photocoagulation involving the foveal center in the study eye
  * Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Day 0
  * History of vitrectomy, submacular surgery, or other surgical intervention for AMD in the study eye
  * Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals) Lesion Characteristics
  * Subfoveal fibrosis or atrophy in the study eye
  * CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
C: Inclusion Criteria:

* Ability to provide written informed consent and comply with study assessments for the full duration of the study
* Age \> 18 years
* Ischemic CRVO within 3 months of enrollment as per the following inclusion criteria
* Three of the following clinical tests must be present to demonstrate ischemic CRVO:

  * VA 20/200 or worse
  * RAPD 0.9 LU or worse
  * Loss of 1-2e isopter on Goldmann Visual field (Kwon et al. 2001)
  * ERG demonstrating b wave amplitude less than 60% of A wave

Exclusion Criteria:

* Angle neovascularization greater than 3 clock hours with IOP over 30 (Neovascular glaucoma)
* Any previous retinal laser photocoagulation to the study eye
* Any previous intravitreal injection in study eye (triamcinolone or other)
* Any previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
* Intracapsular cataract extraction (posterior capsule needs to be present)
* Previous history of retinal detachment in study eye
* Any previous radiation treatments to head/ neck
* Inability to assess iris neovascularization (corneal opacity precluding gonioscopy)
* Significant cardiovascular disease or cancer that would prevent follow-up visits or completion of the 12 month study
* Significant diabetic retinopathy in the fellow eye (diabetic macular edema, proliferative diabetic retinopathy, or high-risk non-proliferative diabetic retinopathy)
* Pregnancy (positive pregnancy test)
* Prior enrollment in any study for vein occlusion in the study eye
* Participation in another simultaneous medical investigator or trial
* Ocular disorders in the study eye that may confound interpretation of study results, including retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME AMD, ocular histoplasmosis, or pathologic myopia)
* Concurrent disease in the study eye that could compromise visual acuity or require medical or surgical intervention during the study period
* Aphakia or absence of the posterior capsule in the study eye
* Previous violation of the posterior capsule is also excluded unless it occurred as a result of YAG laser posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation
* History of idiopathic or autoimmune uveitis in either eye
* Structural damage to the center of the macula in the study eye preexisting to CRVO likely to preclude improvement in visual acuity following the resolution of macular edema, including atrophy of the retinal pigment epithelium, subretinal fibrosis, laser scar(s)
* Vitreomacular traction or epiretinal membrane in the study eye evident biomicroscopically or by OCT
* Ocular inflammation (including trace or above) in the study eye
* Uncontrolled glaucoma (defined as intraocular pressure ≥30 mm Hg despite treatment with anti- medications) or previous filtration surgery in the study eye
* Infectious blepharitis, keratitis, scleritis, or conjunctivitis (in either eye) or current treatment for serious systemic infection
* Spherical equivalent of the refractive error in the study eye of more than -8 diopters myopia (For patients who have had refractive or cataract surgery in the study eye, pre-operative spherical equivalent refractive error of more than -8 diopters myopia is not allowed) Systemic Conditions
* Uncontrolled Blood pressure exceeding diastolic pressure of 100 mm Hg (sitting) during the screening period
* Uncontrolled diabetes mellitus
* Renal failure requiring dialysis or renal transplant
* Premenopausal women not using adequate contraception
* Previous participation in other studies of investigational drugs (excluding vitamins and minerals) within 3 months preceding Day 0
* History of other disease, metabolic dysfunction, physical examination finding, or other findings 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 render the subject at high risk from treatment complications
* INR ≥ 3.0 (e.g. due to current treatment with warfarin). The use of aspirin is not an exclusion.

Other

* History of allergy to fluorescein, not amenable to treatment
* Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
* Inability to comply with study or follow up procedures
* History of allergy to humanized antibodies or any component of the ranibizumab formulation
D: Inclusion Criteria:

* Signed informed consent
* Age \>=50 years
* Eligibility for treatment with PDT using verteporfin in the study eye according to the Visudyne product labeling
* Future treatment with PDT using verteporfin anticipated or expected in the study eye
* Primary or recurrent subfoveal choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) in the study eye
* A classic CNV component (well-demarcated hyperfluorescence boundaries in the early phase of the fluorescein angiogram) that is \>=50% of the total lesion size
* Total lesion size of less than or equal to 5400 um in greatest linear dimension (GLD)
* Best corrected visual acuity, using Early Treatment of Diabetic Retinopathy Study (ETDRS) charts, of 20/40 to 20/320 (Snellen equivalent) in the study eye

Exclusion Criteria:

* Prior treatment with verteporfin, external-beam radiation therapy, or transpupillary thermotherapy (TTT) in the study eye
* Treatment with verteporfin in the non-study eye less than 7 days preceding Day 0
* Previous participation in a clinical trial (for either eye) involving anti angiogenic drugs (pegaptanib, ranibizumab, anecortave acetate, protein kinase C inhibitors, etc.)
* Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye
* Previous subfoveal focal laser photocoagulation in the study eye
* Laser photocoagulation (juxtafoveal or extrafoveal) in the study eye within 1 month preceding Day 0
* History of vitrectomy surgery in the study eye
* History of submacular surgery or other surgical intervention for AMD in the study eye
* Previous participation in any studies of investigational drugs within 1 month preceding Day 0 (excluding vitamins and minerals)
* Subretinal hemorrhage in the study eye that involves the center of the fovea, if the size of the hemorrhage is either \>=50% of the total lesion area or \>=1 disc area (DA) in size
* Subfoveal fibrosis or atrophy in the study eye
* CNV in either eye due to other causes, such as ocular histoplasmosis, trauma, or pathologic myopia
* Retinal pigment epithelial tear involving the macula in the study eye
* Any concurrent intraocular condition in the study eye (e.g., cataract or diabetic retinopathy) that, in the opinion of the Investigator could either: (1) Require medical or surgical intervention during the 24-month study period to prevent or treat visual loss that might result from that condition, or (2) If allowed to progress untreated, could likely contribute to loss of at least 2 Snellen equivalent lines of best corrected visual acuity over the 24-month study period
* Active intraocular inflammation (grade trace or above) in the study eye
* Current vitreous hemorrhage in the study eye
* History of rhegmatogenous retinal detachment or macular hole (Stage 3 or 4) in the study eye
* History of idiopathic or autoimmune-associated uveitis in either eye
* Infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye
* Aphakia or absence of the posterior capsule in the study eye
* Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia
* Intraocular surgery (including cataract surgery) in the study eye within 2 months preceding Day 0
* Uncontrolled glaucoma in the study eye (defined as intraocular pressure \>=30 mmHg despite treatment with anti-glaucoma medication)
* History of glaucoma filtering surgery in the study eye
* History of corneal transplant in the study eye
* Premenopausal women not using adequate contraception
* 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 of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk for treatment complications
* Current treatment for active systemic infection
* History of allergy to fluorescein, not amenable to treatment
* Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed and graded by the central reading center
* Inability to comply with study or follow up procedures

Answer: D