Ignite Creation Date:
2025-12-25 @ 2:13 AM
Ignite Modification Date:
2025-12-31 @ 11:09 AM
Study NCT ID:
NCT00815360
Status:
COMPLETED
Last Update Posted:
2015-03-05
First Post:
2008-12-26
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Ranibizumab and Peripheral Scatter Laser in Patients With Diabetic Macular Edema and Peripheral Nonperfusion
Sponsor:
Retina Associates of Florida, P.A.
Organization:
Study Overview
Official Title:
Ranibizumab (rhuFab V2) and Scatter Laser Photocoagulation in Treatment of Patients With Clinically-significant Diabetic Macular Edema With Peripheral Retinal Nonperfusion (RaScaL)
Status:
COMPLETED
Status Verified Date:
2014-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RaScaL
Brief Summary:
To investigate the role of ranibizumab and angiographically-directed peripheral scatter laser therapy in patients with clinically-significant diabetic macular edema (CSME) and peripheral nonperfusion. We propose a novel treatment of CSME in a subgroup of patients defined by a combination of ultrawide-field angiography (UWFA) and optical coherence tomography (OCT). Within this classification scheme, patients with CSME are subdivided by the presence of: 1) focal macular leakage, 2) vitreomacular interface traction, and/or 3) peripheral nonperfusion. The successful treatment of diabetic macular edema would be dictated by pathophysiology-directed therapy based on this classification.
The subgroup of interest for this clinical trial is characterized by diabetic macular edema, peripheral nonperfusion on UWFA, and the absence of macular traction on OCT. This group of patients has previously not been well recognized or characterized due to limitations in previous, standard angiographic evaluation of the retinal periphery.
We postulate that this subcategory represents one with a high rate of failure of accepted therapies given persistence of the basic pathophysiologic mechanism for CSME, namely ischemia-induced production of Vascular Endothelial Growth Factor (VEGF) from the retinal periphery. This also represents a population of patients with likely recurrence of CSME despite treatment with anti-VEGF therapy alone for the same reason.
The subgroup of interest for this clinical trial is characterized by diabetic macular edema, peripheral nonperfusion on UWFA, and the absence of macular traction on OCT. This group of patients has previously not been well recognized or characterized due to limitations in previous, standard angiographic evaluation of the retinal periphery.
We postulate that this subcategory represents one with a high rate of failure of accepted therapies given persistence of the basic pathophysiologic mechanism for CSME, namely ischemia-induced production of Vascular Endothelial Growth Factor (VEGF) from the retinal periphery. This also represents a population of patients with likely recurrence of CSME despite treatment with anti-VEGF therapy alone for the same reason.
Detailed Description:
Diabetic retinopathy is a leading cause of moderate and severe visual loss in developed countries. It is of paramount socioeconomic impact as the prevalence of diabetes is sharply increasing, diabetic macular edema is the leading cause of vision loss in working age patients, it is a significant cause of vision loss in patients older than 65 years of age, it frequently affects patients bilaterally, and the costs of therapy are increasing.
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy. The pathophysiology of DME is complex and multifactorial. Chronic hyperglycemia, protein kinase C (PKC) formation, free radical accumulation, advanced glycation end-product (AGE) proteins, and ischemia-driven release of vascular endothelial growth factor (VEGF) are some of the better understood factors that contribute to chronic retinal arterial and capillary damage and increased permeability.
The RIDE and RISE Studies demonstrated the superiority of anti-VEGF monotherapy with ranibizumab over sham therapy, when all groups were allowed to receive macular laser therapy after month 3 based on predefined criteria. Furthermore, other studies have demonstrated VEGF inhibitors to be beneficial for DME, either as monotherapy or in combination with macular laser.
The benefit of VEGF antagonists in treating DME validates that the VEGF pathway is a key target. The need for repeated anti-VEGF injections to maintain the benefit of treatment begs the question whether persistent peripheral retinal ischemia may be driving VEGF production in at least a subset of patients with DME. Fluorescein angiographic studies of the mid- and far-periphery of diabetic patients by Shimizu in the 1980's demonstrated areas of peripheral retinal nonperfusion in diabetic patients. These findings have been reproduced and substantiated more recently utilizing a novel, commercially-available imaging system for ultrawide-field angiography (UWFA) that employs a scanning laser ophthalmoscope and an ellipsoidal mirror.
We investigated whether patients with diabetic macular edema associated with peripheral nonperfusion on UWFA would have improved visual acuity, resolution of retinal thickening on OCT, and durability of therapy using a novel strategy of a single intravitreal injection of Ranibizumab, a VEGF-A inhibitor + UWFA-guided peripheral Scatter Laser, or RaScaL. A second goal of the study was to guide DME treatment by the imaging signature of UWFA and OCT.
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy. The pathophysiology of DME is complex and multifactorial. Chronic hyperglycemia, protein kinase C (PKC) formation, free radical accumulation, advanced glycation end-product (AGE) proteins, and ischemia-driven release of vascular endothelial growth factor (VEGF) are some of the better understood factors that contribute to chronic retinal arterial and capillary damage and increased permeability.
The RIDE and RISE Studies demonstrated the superiority of anti-VEGF monotherapy with ranibizumab over sham therapy, when all groups were allowed to receive macular laser therapy after month 3 based on predefined criteria. Furthermore, other studies have demonstrated VEGF inhibitors to be beneficial for DME, either as monotherapy or in combination with macular laser.
The benefit of VEGF antagonists in treating DME validates that the VEGF pathway is a key target. The need for repeated anti-VEGF injections to maintain the benefit of treatment begs the question whether persistent peripheral retinal ischemia may be driving VEGF production in at least a subset of patients with DME. Fluorescein angiographic studies of the mid- and far-periphery of diabetic patients by Shimizu in the 1980's demonstrated areas of peripheral retinal nonperfusion in diabetic patients. These findings have been reproduced and substantiated more recently utilizing a novel, commercially-available imaging system for ultrawide-field angiography (UWFA) that employs a scanning laser ophthalmoscope and an ellipsoidal mirror.
We investigated whether patients with diabetic macular edema associated with peripheral nonperfusion on UWFA would have improved visual acuity, resolution of retinal thickening on OCT, and durability of therapy using a novel strategy of a single intravitreal injection of Ranibizumab, a VEGF-A inhibitor + UWFA-guided peripheral Scatter Laser, or RaScaL. A second goal of the study was to guide DME treatment by the imaging signature of UWFA and OCT.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: