Patients with a history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Patients with a history of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension)
Patients who meet any of the following exclusion criteria related to ocular disease will be excluded from study entry:\r\n* Known risk factors for ocular toxicity, consisting of any of the following:\r\n** History of serous retinopathy\r\n** History of retinal vein occlusion (RVO)\r\n** Evidence of ongoing serous retinopathy or RVO at screening
History or current evidence/risk of retinal vein occlusion (RVO)
History or current evidence of retinal vein occlusion or current risk factors for retinal vein occlusion (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Patients with known history or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR) are not eligible:\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg\r\n* NOTE: ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration
Patients must not have history of retinal vein occlusion (RVO)
Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible
Comorbid conditions\r\n* No evidence of active bleeding, bleeding diathesis, or hemoptysis (>= 1/2 teaspoon of red blood) =< 8 weeks prior to registration\r\n* No evidence of intracranial hemorrhage =< 4 weeks prior to registration\r\n* Patients who have experienced thromboembolic event within 6 months prior to registration must be on stable therapeutic anticoagulation for at least 4 weeks prior to registration\r\n* No symptomatic congestive heart failure (New York Heart Association class II, III, or IV) within 6 months prior to registration\r\n* No current unstable angina or uncontrolled arrhythmia\r\n* No uncontrolled hypertension at time of registration (blood pressure [BP] > 150/95 despite antihypertensive therapy)\r\n* No known history of prolonged QT syndrome\r\n* No known history of ventricular arrhythmia within 6 months of registration\r\n* No known history of uveitis or iritis =< 4 weeks prior to registration\r\n* No known history of or evidence of retinal pathology that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration within 12 months of registration
Patients with a previously documented retinal vein occlusion
Patients with a history of any retinal disorders (e.g., retinal detachment, diabetic retinopathy, retinal hemorrhage, macular degeneration).
History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at baseline
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, RVO (retinal vein occlusion), or neovascular macular degeneration; the risk factors for RVO are listed below; patients should be excluded if they have the following current conditions: \r\n* Uncontrolled glaucoma with intra-ocular pressures > 21 mmHg \r\n* Serum cholesterol > grade 2 \r\n* Hypertriglyceridemia > grade 2 \r\n* Hyperglycemia (fasting) > grade 2
History of retinal vein occlusion, neurosensory retinal detachment, or neovascular macular degeneration. Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment.
Patients with history of retinal vein oclusion.
History of current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma; intra-ocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
A history or current evidence of retinal vein occlusion (RVO) including:\r\n* History of RVO or\r\n* Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg as measured by tonography
History of prior or current retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
Participants with evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Participants with a history of or current evidence of retinal vein occlusion or retinal pigment epithelial detachment
Have a degenerative retinal disease. Retinal diseases that require a subject's exclusion include: glaucoma, hereditary retinal diseases such as retinitis pigmentosa; retinal arterial occlusive disease; and retinal disease with advanced scarring, to include age-related macular degeneration and myopic degeneration with geographic atrophy.
Patients with a history or current evidence of CSR (central serous retinopathy), RVO (rential vein occlusion), or ophthalmopathy present at baseline that would be considered a risk factor for CSR or RVO
A history of current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Ophthalmological conditions as follows:\r\n* Current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion\r\n* Uncontrolled glaucoma (irrespective of intraocular pressure [IOP])
Subjects with any retinal abnormalities, including subjects with diabetic retinopathy, macular degeneration, or other known forms of retinal degenerative disease
Known history of retinal vein occlusion (RVO).
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for retinal vein occlusion (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, etc.)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: History of retinal degenerative disease
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Presence of neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration on screening ophthalmologic exam
EXPANDED ACCESS COHORT: Presence of neurosensory retinal detachment or retinal vein occlusion (RVO) on screening ophthalmologic exam
Participants with evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Complete portal vein occlusion
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration Cardiac Exclusion Criteria:
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
Have history or findings of central or branch retinal artery or venous occlusion with significant vision loss or other retinal diseases that cause current visual impairment or would likely cause visual impairment over the time period of the study.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Known risk factors for ocular toxicity, consisting of any of the following:\r\n* presence of serous retinopathy within 6 months of protocol enrollment\r\n* presence of retinal vein occlusion (RVO) within 6 months of protocol enrollment.
History of or evidence of retinal pathology on baseline ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
STRATUM B: Participants with retinal vein occlusion (RVO)
History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration. Patients should be excluded if they have the following risk factors for RVO:\r\n* History of serous retinopathy.\r\n* History of retinal vein occlusion (RVO).\r\n* Evidence of ongoing serous retinopathy or RVO at baseline.
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg.
Presence of retinal disease in the eye that is not due to neovascular age-related macular degeneration (nAMD; eg, significant diabetic retinopathy, glaucomatous retinal atrophy, retinal detachment).
Any corneal or retinal abnormality likely to increase the risk of eye toxicity, such as:\r\n* Current corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration\r\n* Uncontrolled glaucoma despite standard of care therapy\r\n* Diabetic retinopathy with macular edema\r\n* Known active wet, age-related macular degeneration (AMD)\r\n* Known central serous retinopathy (CSR) or retinal vascular occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration; patients will be excluded from study participation if they are currently known to have any of the following risk factors for RVO:\r\n* Glaucoma with intraocular pressure >= 21 mmHg\r\n* Grade >= 2 serum cholesterol (patients with a history of elevated cholesterol controlled with lipid lowering medication to grade =< 1 are eligible)\r\n* Grade >= 2 hypertriglyceridemia (patients with a history of elevated cholesterol controlled with lipid lowering medication to grade =< 1 are eligible)\r\n* Grade >= 2 or symptomatic hyperglycemia (fasting); hyperglycemia may be corrected with medications to grade =< 1\r\n* Grade >= 2 uncontrolled hypertension (patients with a history of hypertension controlled with anti-hypertensive medication to grade =< 1 are eligible)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
Patients will be excluded if they currently have the following risk factors for retinal vein occlusion (RVO): (1) uncontrolled glaucoma with intra-ocular pressures >= 21 mmHg (2) serum cholesterol >= grade 2 (3) hypertriglyceridemia >= grade 2 (4) hyperglycemia (fasting) >= grade 2
Ophthalmological conditions as follows: current or past history of retinal pigment epithelial detachment (RPED)/central serous retinopathy (CSR) or retinal vein occlusion; or intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma (irrespective of IOP)
History of or current evidence of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED\r\n* Current evidence of visible retinal pathology as assessed by pre-study ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of visual field defects, and/or intraocular pressure > 21 mm Hg
Patients will not be eligible if they have a history of retinal vein or artery occlusion
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
A history or current evidence of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a high risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
Ocular:\r\n* History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusions (RVO), or neovascular macular degeneration\r\n* The risk factors for RVO are listed below; patients should be excluded if they have the following current conditions:\r\n** Uncontrolled glaucoma with intra-ocular pressures > 21 mmHg\r\n** Serum cholesterol >= grade 2\r\n** Hypertriglyceridemia >= grade 2\r\n** Hyperglycemia (fasting) >= grade 2
Has a history of RVO.
History of or evidence of retinal pathology or ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
Patients with known significant ophthalmologic conditions (uncontrolled glaucoma, history of retinal vein occlusion or retinal detachment, excluding patients with longstanding findings secondary to existing conditions) are not eligible
History or current evidence/risk of retinal vein occlusion (RVO)
Ophthalmological conditions as follows: \r\n• Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure) \r\n• Current or past history of central serous retinopathy or retinal vein occlusion
History of retinal degenerative disease, history of uveitis, history of retinal vein occlusion (RVO), or any eye condition that would be considered a risk factor for RVO or has medically relevant abnormalities identified on screening ophthalmologic examination
A history of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
Patients with macular edema, retinal vein occlusion or retinal hemorrhage are excluded
History of central serous retinopathy (CSR) or retinal vein occlusion (RVO), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
Patients with the following ophthalmological findings/conditions:\r\n* Intraocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intraocular pressure)\r\n* Current or past history of central serious retinopathy or retinal vein occlusion
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm mercury (Hg)
History or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e., uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO)
Ophthalmological conditions as follows:\r\n* Intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure)\r\n* Current or past history of central serous retinopathy or retinal vein occlusion
Portal vein occlusion
History of or current evidence / risk of retinal vein occlusion (RVO) central serous retinopathy (CSR), or glaucoma with intraocular pressures ? 21 mmHg or other pre-existing ocular conditions that may put the patient at risk for ocular toxicities
Current diagnosis of any retinal detachment, retinal pigment epithelial detachment (RPED), serous retinopathy or retinal vein occlusion
A history of retinal vein occlusion (RVO) or risks factors for RVO
History of retinal disease as defined in the protocol.
History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
Ocular exclusion criteria:\r\n* History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion or neovascular macular degeneration\r\n* Patients will be excluded if they have the following risk factors for retinal vein occlusion: Uncontrolled glaucoma with intraocular pressure >= 21 mmHg. Serum cholesterol >= grade 2. Hypertriglyceridemia >= grade 2. Hyperglycemia (fasting) >= grade 2
Ophthalmologic conditions, including any of the following:\r\n* Current or past history of central serous retinopathy\r\n* Current or past history of retinal vein occlusion\r\n* Intraocular pressure (IOP) > 21 mmHg or uncontrolled glaucoma
History of retinal vein occlusion (RVO)
History of retinal vein occlusion (RVO)
History or current evidence or retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
History of retinal degenerative disease
History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/CSCR, RVO, or neovascular macular degeneration
TREATMENT: Patients with a history or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes), are ineligible to receive treatment with trametinib DMSO; visible retinal pathology (as assessed by ophthalmic exam) that is considered a risk factor for RVO or RPED includes evidence of new optic disc cupping or new visual field defects, or intraocular pressure > 21 mm Hg
History of or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
History of retinal vein occlusion (RVO)
Central serous retinopathy (CSR) including presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes); or visible pathology (e.g., evidence of optic disc cupping, evidence of new visual field defects on automated perimetry, or intraocular pressure > 21 mmHg as measured by tonography) as assessed by ophthalmic examination
Patients must not have any of the following ophthalmological criteria: current evidence or previous history of retinal pigmented epithelium detachment (RPED); previous laser treatment or intra-ocular injection for treatment of macular degeneration; current evidence or previous history of dry or wet age-related macular degeneration; current evidence or previous history of retinal vein occlusion (RVO); current evidence or previous history of retinal degenerative diseases (e.g. hereditary); or current evidence or previous history of any other clinically relevant chorioretinal defect
Patients must not have any of the following ophthalmological criteria: current evidence or previous history of retinal pigmented epithelium detachment (RPED); previous laser treatment or intra-ocular injection for treatment of macular degeneration; current evidence or previous history of dry or wet age-related macular degeneration; current evidence or previous history of retinal vein occlusion (RVO); current evidence or previous history of retinal degenerative diseases (e.g. hereditary); or current evidence or previous history of any other clinically relevant chorioretinal defect; patients must have an eye exam performed within 28 days prior to Step 2 re-registration; patients with uncontrolled glaucoma or intra-ocular pressure >= 21 mm Hg at screening should be referred for ophthalmological management and the condition controlled prior to crossover registration
History or current evidence/risk of visual loss syndromes, including but not limited to retinal vein occlusion (RVO), retinal detachment, macular degeneration, or visual migraine headaches
Known ophthalmological conditions as follows: intra-ocular pressure > 21 mmHg, or uncontrolled glaucoma (irrespective of intra-ocular pressure); current or past history of central serous retinopathy or retinal vein occlusion
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED):\r\n* History of RVO or RPED, or predisposing factors to RVO or RPED (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO)
Patient must not have a history of retinal vein occlusion (RVO)
Retinal disease or a history of retinal disease or detachment
CLINICAL/LABORATORY CRITERIA: Patients must not have untreated or unresolved retinopathy or have a history (or current evidence) of retinal vein occlusion determined by an ophthalmology exam within 42 days prior to registration
Retinal disease (e.g. retinitis pigmentosa including Mertk mutations), retinal hemorrhage or any disorder which may inhibit follow up for retinal toxicity
Patients with a history or current evidence/risk of retinal vein occlusion (RVO)
For participants to be enrolled into the vemurafenib+cobimetinib+ atezolizumab cohorts: history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or major predisposing factors to CSR or RVO (e.g. uncontrolled glaucoma or ocular hypertension) in the opinion of the study ophthalmologist
History of retinal degenerative disease
History of predisposition to retinal vein occlusion or central serous retinopathy
Patients have a history or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO) or predisposing factors to CSR or RVO (i.e. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
History of predisposition to retinal vein occlusion or central serous retinopathy
Evidence of visible retinal pathology on screening ophthalmologic examination that places the participant at an unacceptable risk for ocular toxicity, such as risk factors for retinal vein occlusion, related to PD-0325901
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) or predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, history of hyperviscosity or hypercoagulability syndromes; visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mm Hg
History of retinal vein occlusion (RVO)
History of retinal vein occlusion
Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for RVO
Has retinal degenerative disease
History of or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or history of retinal degenerative disease
Patients with known history or current evidence of retinal vein occlusion (RVO) are not eligible:\r\n* History of RVO, or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mmHg\r\n** NOTE: Ophthalmic exam is required for all patients; exam must be obtained within 28 days prior to registration
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
Patients with a history or current known evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO) or ophthalmopathy at baseline that would be considered a risk factor for CSR or RVO
A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
History of or current evidence of retinal vein occlusion (RVO) or risk factors of RVO
History of retinal vein occlusion (RVO)
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED): \r\n* Predisposing factors to RVO or RPED (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or RPED such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects\r\n** Intraocular pressure > 21 mm Hg
Patients with a known history of retinal vein occlusion (RVO) or central serous retinopathy (CSR), or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyper viscosity or hypercoagulability syndromes)
Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as: \r\n* Evidence of new optic disc cupping \r\n* Evidence of new visual field defects \r\n* Intraocular pressure > 21 mm Hg as measured by tonography
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR)
A history or current evidence of retinal vein occlusion (RVO).
History or current evidence/risk of retinal vein occlusion (RVO)
History of central serous retinopathy or retinal vein occlusion
Patients with baseline risk factors for central serous retinopathy or retinal vein occlusion such as evidence of new optic disc cupping, evidence of new visual field defects, and intraocular pressure > 21 mmHg
History or current evidence/risk of retinal vein occlusion (RVO)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration; the risk factors for RVO are listed below; patients should be excluded if they have the following conditions:\r\n* Uncontrolled glaucoma with intra-ocular pressures > 21mmHg\r\n* Serum cholesterol >= grade 2\r\n* Hypertriglyceridemia >= grade 2\r\n* Hyperglycemia (fasting) >= grade 2
Evidence of a retinal vein occlusion on ophthalmological exam or a history of retinal vein occlusion
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
History or current evidence of retinal vein occlusion (RVO) or central serous retinopathy (CSR).
History or current evidence of retinal pigment epithelial detachment (RPED), retinal vein occlusion (RVO), or predisposing factors to RPED or RVO (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled diabetes mellitus, hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
Clinically significant cardiovascular disease, defined as any of the following conditions: i. Uncontrolled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg) ii. Prior history of hypertensive crisis or hypertensive encephalopathy iii. Myocardial infarction within 6 months iv. Unstable angina v. New York heart association grade II or greater congestive heart failure (Appendix C) vi. Serious cardiac arrhythmia requiring medication vii. LVEF < 50% or below institutional limit of normal f) History of stroke of TIAs within 6 months prior to Day 1 g) Grade II or greater peripheral vascular disease within 1 year prior to study entry or other significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 h) Serious, non-healing wound, active ulcer, or untreated bone fracture i) History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1 j) Known hypersensitivity to any component of bevacizumab k) Known CNS disease, except for stable or regressing brain metastases. l) Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation) m) Psychiatric illness/social situations that would limit compliance with study requirements. n) Significant ocular issues including history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration. The risk factors for RVO are listed below. Patients should be excluded if they have the following conditions:
Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis
Predisposing factors to retinal vein occlusion (RVO)
History of RVO, neurosensory retinal detachment, or neovascular macular degeneration
A history or current evidence/risk of retinal vein occlusion or central serous retinopathy
A history or current evidence/risk of Retinal Vein Occlusion (RVO) or Central Serous Retinopathy (CSR) including: History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes); or Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as: Evidence of new optic disc cupping; Evidence of new visual field defects; Intraocular pressure >21 mmHg as measured by tonography.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
A history or current evidence/risk of retinal vein occlusion or retinal pigment epithelial detachment - specific criteria have to be met.
History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioetinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration Patients will be excluded if they currently have either of the following conditions which have been identified as risk factors for CSCR:
The patient has retinal degenerative disease, history of uveitis, or history of retinal vein occlusion, or history of retinal detachment, or has medically relevant abnormalities identified on screening ophthalmologic examination.
History or current evidence/risk of retinal vein occlusion (RVO) or retinal pigment epithelial detachment (RPED) in the eye unaffected by uveal melanoma
The subject has a history of retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), uveitis or retinal vein occlusion (RVO), or has other relevant abnormalities identified on screening opthalmologic examination, which may increase the risk of serous retinal detachment (SRD) or RVO.
History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes).
A history or current evidence/risk of retinal vein occlusion (RVO) or Central serous retinopathy (CSR) including
Visible retinal pathology as assessed by ophthalmic examination that is considered a risk factor for RVO or CSR such as evidence of new optic disc cupping; Evidence of new visual field defects on automated perimetry; Intraocular pressure >21 mmHg as measured by tonography
History or concurrent evidence of retinal vein occlusion (RVO) or current risk factors for RVO.
History of or current evidence of retinal vein occlusion (RVO).
Unacceptable ocular/retinal conditions
History of retinal vein occlusion, central serous retinopathy or glaucoma.
Visible retinal pathology as assessed by ophthalmologic exam that is considered a risk factor for retinal vein occlusion or central serous retinopathy.
No underlying ocular/retinal pathology.
History or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
History of retinal degenerative disease
A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR) including:\r\n* Presence of predisposing factors to RVO or CSR (e.g., uncontrolled glaucoma or ocular hypertension, uncontrolled hypertension, uncontrolled diabetes mellitus, or a history of hyperviscosity or hypercoagulability syndromes)
History or evidence of retinal pathology according to protocol-defined criteria, including serous retinopathy
Patients with a history of retinal disease
History or current evidence/risk of retinal vein occlusion (RVO)
GROUP 2 (trametinib arm): History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes).\r\n* Visible retinal pathology as assessed by ophthalmic exam that is considered a risk factor for RVO or CSR such as:\r\n** Evidence of new optic disc cupping\r\n** Evidence of new visual field defects  \r\n** Intraocular pressure > 21 mm Hg
History or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy (CSR):\r\n* History of RVO or CSR, or predisposing factors to RVO or CSR (e.g. uncontrolled glaucoma or ocular hypertension, uncontrolled systemic disease such as hypertension, diabetes mellitus, or history of hyperviscosity or hypercoagulability syndromes)
Evidence of visible retinal pathology as assessed by ophthalmologic examination that is considered a risk factor for retinal vein thrombosis or neurosensory retinal detachment
History of retinal vein occlusion (RVO), neurosensory retinal detachment, or neovascular macular degeneration