Widefield Angiography Guided Targeted-retinal Photocoagulation Combined With Anti VEgf Intravitreal Injections for the Treatment of Ischemic Central Retinal Vein Occlusion, Hemi Retinal Vein Occlusion, and Branch Retinal Vein Occlusion

Phase 4

Completed

Conditions: Central Retinal, Hemi Retinal & Brach Retinal Vein Occlusions

Interventions: Drug: 0.5mg Ranibizumab
Procedure: Targeted Pan Retinal Photocoagulation

Registration Number: NCT01710839

Lead Sponsor: Charles C Wykoff, PhD, MD

Brief Summary: To see if Lucentis 0.5mg combined with Targeted Pan Retinal photocoagulation will decrease the total number of intravitreal injections in a year for ischemic central retinal vein occlusion, hemi-retinal vein occlusions and branch retinal vein occlusions compared to standard of care

Detailed Description: The WAVE trial is a phase IV, open label, 12-month trial of intravitreal ranibizumab 0.5 mg in patients (n=30) with ischemic CRVO, HRVO and BRVO who have been previously treated with ranibizumab or any other anti-VEGF intravitreal injection therapy, who are incomplete responders to 2 or more consecutive intravitreal anti-VEGF injections in the past 4 months. Randomization is 1:4, 1=control, ranibizumab only, 4=treatment arm. In total, 6 subjects will be randomized to control and 24 randomized to treatment arm.

Cohort 1- 24 Subjects previously treated Patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Wide field angiography guided peripheral targeted-retinal photocoagulation (TRP), will be divided into 2 sessions if needed, one at the 2 weeks post injection visit and another later at M4/V7, if repeat wide field angiogram indicates areas not sufficiently treated in the first TRP session

Cohort 2- 6 Subjects, previously treated patients will receive 6 doses of ranibizumab 0.5 mg, followed by PRN intravitreal injection of ranibizumab 0.5 mg based on pre-defined retreatment criteria for up to 11 total injections.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Age > 18 years
Visual acuity between 20/25 and 20/800, ETDRS best corrected visual acuity
Ability to provide written informed consent and comply with study assessments for the full duration of the study

Patients previously treated with any ITV anti-VEGF:

• With at least 2 consecutive monthly intravitreal injections of anti-VEGF medications with presence of persistent or recurrent macular edema in the past 4 months

Exclusion Criteria

IOP over 30 mm Hg
Any previous retinal laser photocoagulation to the study eye
Previous intravitreal injection in the study eye of any corticosteroid treatment
Previous vitrectomy in study eye (posterior or anterior associated with vitreous loss in cataract surgery)
Intracapsular cataract extraction
Any previous radiation treatments to head/neck that the principal or sub investigator feels is clinically relevant
Inability to assess iris or angle 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)
Participation in another simultaneous medical investigator or trial
Ocular disorders or concurrent disease in the study eye that may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention, including history of retinal detachment, macular hole, or choroidal neovascularization of any cause (e.g., DME, AMD, ocular histoplasmosis, or pathologic myopia)
Structural damage to the center of the macula in the study eye prior to CRVO, HRVO and BRVO 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 clinically significant epiretinal membrane in the study eye evident biomicroscopically or by OCT (vitreomacular attachment OK)
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, preoperative spherical equivalent refractive error of more than -8 diopters myopia is not allowed)
Uncontrolled Blood pressure: defined as systolic pressure > 180mmHg and/or diastolic pressure of >110 mm Hg (sitting) during the screening period
Uncontrolled diabetes mellitus
Renal failure requiring dialysis or renal transplant
Pregnancy (positive pregnancy test) or lactation
Premenopausal women not using adequate contraception. The following are considered effective means of contraception: surgical sterilization or use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an IUD, or contraceptive hormone implant or patch.
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
History of allergy to fluorescein, not amenable to treatment
Inability to obtain fundus photographs or fluorescein angiograms of sufficient quality to be analyzed by the principal investigator (PI) and/or the sub-investigator.
History of allergy to humanized antibodies or any component of the ranibizumab formulation

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Targeted Pan Retinal laser combined with 0.5mg ranibizumab	Targeted Pan Retinal Photocoagulation	Cohort 1 (n=24), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses of 0.5 mg ranibizumab followed by PRN treatment with ranibizumab 0.5 mg; after receiving the first loading dose of ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) based on 200° wide field angiography with possibility of a second session of TRP at M4/M7, if non-perfusion persists based on angiogram.The 200°wide field angiography will indicate areas of peripheral ischemia which will be selectively treated, preserving areas of more perfused retina.
Targeted Pan Retinal laser combined with 0.5mg ranibizumab	0.5mg Ranibizumab	Cohort 1 (n=24), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses of 0.5 mg ranibizumab followed by PRN treatment with ranibizumab 0.5 mg; after receiving the first loading dose of ranibizumab, the subject will have peripheral targeted-retinal photocoagulation (TRP) based on 200° wide field angiography with possibility of a second session of TRP at M4/M7, if non-perfusion persists based on angiogram.The 200°wide field angiography will indicate areas of peripheral ischemia which will be selectively treated, preserving areas of more perfused retina.
Ranibizumab 0.5mg	0.5mg Ranibizumab	Cohort 2 (n=6), previously treated with at least 2 consecutive or more intravitreal injections of any anti-VEGF agent with persistent or recurrent macular edema will receive 6 loading doses followed by PRN monthly treatment with ranibizumab 0.5 mg.

Primary Outcome Measures

Name	Time	Method
Total Number of Intravitreal Injections Over a 12 Month Period	12 months	Assess the number of intravitreal injections over 12 months.
Visual Acuity	12 month period	Evaluate the mean change from baseline in ETDRS best-corrected visual acuity at 12 months. The ETDRS protocol is a widely accepted international standard for macular laser photocoagulation treatment. A higher score represents better functioning.

Secondary Outcome Measures

Name	Time	Method
Foveal Avascular Zone	12 months	Assess change in foveal avascular zone area and largest diameter, measured during the early phase of the angiogram
Visual Field	6 and 12 Months	Goldman Visual Field changes at 6 and 12 months from baseline. Goldmann perimetry is a method used to map a patient's field of vision (central and peripheral). Changes will be assessed by manual digital quantification of GVF plots.
Adverse Events	12 months	Incidence and severity of adverse events (ocular and non-ocular).
Retinal Ischemia	12 month period	Quantify change in area of perfused and ischemic retina.
Neovascularization of the Iris, Optic Nerve and Elsewhere	12 months	Percent of patients that develop neovascularization of the iris, optic nerve and/or elsewhere.
Central Foveal Outcome	12 months	Mean change in Central Foveal Volume on High Resolution OCT.
Aqueous VEGF Levels	12 Months	VEGF, other cytokines and ranibizumab levels in aqueous and serum samples at randomization and at the exit or early termination visit.

Trial Locations

Locations (2): Retina Consultants of Houston/The Medical Center
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Houston, Texas, United States
Retina Consultants of Houston
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The Woodlands, Texas, United States