Behind the Lab Door

Phase 1/2 prospective, randomized, double-blinded study of intravitreal anti-VEGF therapy combined with proton beam radiation versus sham irradiation in treating exudative age-related macular degeneration (PBAMD2)

Institution: University of California Davis Eye Center

Author/principal investigator: Susanna S. Park, MD, PhD

Abstract/statement of the trial’s goals:

The PBAMD2 study is a phase 1/2 study designed to further explore the safety and efficacy of low-dose proton beam irradiation combined with intravitreal anti-VEGF therapy — Lucentis (ranibizumab, Genentech) or Avastin (bevacizumab, Genentech) in treating eyes with newly diagnosed exudative age-related macular degeneration.

ClinicalTrials.gov identifier: NCT01213082

Study population: 45

Inclusion criteria:

Ability to provide written informed consent and comply with study assessments for the full duration of the study
Age: 50 years or older
Able to maintain follow-up for at least 24 months
Women must be postmenopausal without a period for at least 1 year
Diagnosed with age-related macular degeneration with active subfoveal choroidal neovascular membrane, newly diagnosed or treated with first dose of anti-VEGF therapy within 6 weeks of enrollment
Visual acuity: 20/40 to 20/400
Lesion size: less than 12 disc area
Submacular hemorrhage less than 75% of total lesion and not involving foveal center
Submacular fibrosis less than 25% of total lesion
Candidate for intravitreal anti-VEGF therapy

Exclusion criteria:

Prior enrollment in the study
Pregnancy (positive pregnancy test) or lactation
Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Participation in another simultaneous medical investigation or trial
Previous treatment with macular photodynamic therapy or thermal laser in the study eye
Anti-VEGF therapy in study eye more than 6 weeks before enrollment
Intravitreal or sub-Tenon’s Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) within 6 months
Intraocular surgery within 3 months or expected in the next 6 months
Current or planned participation in other experimental treatments for wet AMD
Other concurrent retinopathy or optic neuropathy
Other causes of choroidal neovascular membrane, ie, myopic degeneration or ocular histoplasmosis
Significant media opacity precluding adequate view of the fundus for exam, photography or optical coherence tomography
History of radiation therapy to the head or study eye
Diabetes mellitus or hemoglobin A1c greater than 6
Head tremor or history of claustrophobia precluding positioning for proton irradiation
Inability to maintain steady fixation with either eye
History of malignancy treated within 5 years
Allergy to fluorescein dye

Enrollment status: Currently recruiting participants:

University of California Davis Eye Center, Sacramento, Calif.
Mather VA Hospital, Sacramento, Calif.

A note from the institution regarding the value of this trial:

Radiation combined with anti-VEGF therapy may have a synergistic effect on eyes with exudative AMD. Among the various modes of radiation delivery to the macula, proton beam provides advantages in that vitrectomy is not needed and radiation can be delivered more precisely. A pilot study investigating proton beam combined with ranibizumab showed no safety concerns after 3 years and possible sustained treatment effect in eyes with newly diagnosed exudative AMD. This ongoing phase 1/2 double-masked, prospective, sham-controlled study will randomize subjects 1:1:1 to 24 Gy proton, 16 Gy proton or sham irradiation, administered once in two fractions, 24 hours apart. Each eye will be treated with three monthly doses of intravitreal ranibizumab or bevacizumab. Re-treatment with anti-VEGF will be based on new or increasing intraretinal or subretinal fluid on OCT, new macular hemorrhage, or decrease in vision of two or more lines noted on monthly follow-up examination.

Intra-arterial thrombolysis for severe recent central retinal vein occlusion

Institution: Weill Cornell Medical College

Author/principal investigator: Y. Pierre Gobin, MD

Abstract/statement of the trial’s goals:

Study hypothesis: Injection of tPA, a thrombolytic drug, into the ophthalmic artery in patients with recent severe central retinal vein occlusion (CRVO) may reopen the central retinal vein and improve retinal blood flow, which may in turn improve visual acuity and prevent the long-term complications of the disease.

Experimental intervention: An outpatient procedure during which the ophthalmic artery is selectively catheterized with a small plastic tube called a microcatheter introduced from the artery of the leg and infused with tPA over 2 hours.

ClinicalTrials.gov identifier: NCT01581411

Study population: Five

Inclusion criteria:

Severe CRVO diagnosed on presence of relative afferent pupillary defect or visual acuity of 20/200 or worse
Symptom onset within 2 weeks
Age: older than 18 years
Patient able and willing to give informed consent

Exclusion criteria:

Futile intervention: no light perception, absence of perfusion on fluorescein angiography
Contraindication to thrombolysis: active or recent (1 month) internal bleeding, cerebrovascular accident, major organ surgery, major trauma; intracranial neoplasm or vascular malformation, known bleeding diathesis, severe uncontrolled arterial hypertension, pregnancy (women of childbearing age must have a negative serum pregnancy test), or any other condition that in the opinion of the investigators would preclude the use of thrombolytic agents
High-risk catheterization: history of stroke or transient ischemic attack; carotid bruit or known carotid occlusive disease; any cardiovascular condition that in the opinion of the investigators may increase the risk of catheterization of the ophthalmic artery
Ocular criteria: intraocular neovascularization (secondary to any etiology), vitreous hemorrhage, inflammatory eye disease, any condition that precludes fundus photography or fluorescein angiography

Enrollment status: Currently recruiting participants:

Weill Cornell Medical College/ New York Presbyterian Hospital, New York