Diabetic Retinopathy Clinical Trial
Official title:
Lucentis in the Treatment of Macular Edema - A Phase II, Single Center, Randomized Study to Evaluate the Efficacy of Ranibizumab Versus Focal Laser Treatment in Subjects With Diabetic Macular Edema
This study will evaluate the clinical efficacy of intra-vitreal injections of Ranibizumab (Lucentis) in the treatment of Diabetic Macular Edema as compared to grid/focal laser.
Diabetic macular edema (DME) results from abnormal leakage of macromolecules into the
extracellular space from microaneurysms and incompetent blood vessel walls due to small
vessel damage from high blood glucose levels. Oncotic forces then allow water into the
extracellular space. Abnormalities in the retinal pigment epithelium (RPE) may reduce normal
outflow of fluid from the retina to the underlying choriocapillaris via the pump mechanism
(Ferris et al. 1984). This leads to retinal edema in the macula with accompanying loss of
vision. There is evidence suggesting that vascular endothelial growth factor (VEGF) plays a
part in vessel wall permeability with subsequent retinal edema (Aiello et al. 1997).
Studies demonstrate that tight junctions in the vessel walls were shown to be regulated by
VEGF and VEGF increases vascular permeability (Anticliff et al. 1999). The healthy human
retina contains little or no VEGF. Hypoxia, a component of diabetic retinopathy, causes
upregulation of VEGF in the retina (Vinores et al. 1997). Binding VEGF with an antibody
specific for VEGF may inhibit resultant edema thus preventing and possibly reversing loss of
vision.
Diabetic retinopathy is the leading cause of blindness in people aged 20-74 years,
accounting for 8% of all cases of legal blindness and 12% of the newly blind (Klein 1995). A
common complication of all forms of diabetes mellitus, diabetic retinopathy is present in
over 2.5% of the U.S. population, or more than 5.3 million people aged 18 or older (Prevent
Blindness American 2002).
Three forms of retinopathy are commonly recognized in association with all forms of diabetes
mellitus: 1) non-proliferative diabetic retinopathy (NPDR), 2) proliferative diabetic
retinopathy (PDR), and 3) diabetic macular edema (DME).
NPDR is characterized by ophthalmoscopically visable abnormalities that include
microaneurysms, intraretinal hemorrhages, exudates, retina nerve fiber layer infarcts
(cotton-wool spots), and, in more severe cases, venous beading and intraretinal
microvascular abnormalities (IRMA).
Over time, NPDR may progress to more severe PDR, the hallmark of which is neovascularization
on the surface of the retina, optic disc, or iris, and angle structures in the front of the
eye. PDR is associated with a high risk of visual morbidity arising from vitreous
hemorrhage, traction retinal detachment, and neovascular glaucoma (Diabetic Retinopathy
Research Group 1979).
DME, the third form of diabetic retinopathy, is characterized by swelling of the central
part of the retina that mediates high-resolution vision. DME frequently coexists with and is
superimposed upon NPDR or PDR. When the area of swelling is located more than 1 disc
diameter (approximately 1500 mm) away from the center of the fovea, the swelling constitutes
a low threat to visual acuity and is regarded as non-clinically significant macular edema
(Early Treatment Diabetic Retinopathy Study [ETDRS] Research Group 1985). Vision
deteriorates when DME involves the foveal center. DME that either directly involves the
fovea or is at high risk of doing so is referred to as Clinically Significant Macular Edema
(CSME) (ETDRS Research Group 1985).
When the center of the fovea is involved by CSME, the DME is referred to as CSME with center
involvement (CSME-CI), as opposed to CSME without center involvement (ETDRS Research Group
1987).
The natural history of untreated CSME-CI is particularly poor. The ETDRS demonstrated that
over a 3-year period, 33% of subjects with CSME-CI lose >15 letters of visual acuity on the
standardized ETDRS Visual Acuity Chart (Ferris et al. 1982) compared with 23% of CSME
subjects without center involvement (ETDRS Research Group 1987). Such a degree of visual
acuity change is equivalent to doubling of the visual angle or greater. The ETDRS did not
discriminate between subtypes of diabetes mellitus.
Although laser photocoagulation in CSME-CI was shown to reduce the proportion of subjects
losing > 15 letters from 33% to 13% over 3 years, 13% of subjects nevertheless continued to
double their visual angle or do worse. Moreover, in subjects with CSME initially without
center involvement, over 3 years, 12% lose > 15 letters despite laser treatment, presumably
because edema eventually involves the center of the fovea (i.e., the subjects convert to
CSME-CI). Thus, while laser is an effective tool in the treatment of CSME, there is a
considerable unmet clinical need for CSME-CI.
This study is designed to compare the effectiveness of intra-vitreal Ranibizumab to current
standard of care.
;
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03660371 -
ILM Peeling in PDR Patients Undergoing PPV for VH
|
N/A | |
Completed |
NCT03660345 -
PPV With Internal Limiting Membrane Peeling for Treatment-Naïve DME
|
Phase 3 | |
Completed |
NCT03660384 -
Silicone Oil Versus Gas in PDR Patients Undergoing Vitrectomy
|
N/A | |
Completed |
NCT04905459 -
ARDA Software for the Detection of mtmDR
|
||
Active, not recruiting |
NCT04271709 -
Manhattan Vision Screening and Follow-Up Study (NYC-SIGHT)
|
N/A | |
Recruiting |
NCT03713268 -
Intraoperative OCT Guidance of Intraocular Surgery II
|
||
Completed |
NCT05022615 -
Comparing 3 Imaging Systems
|
||
Completed |
NCT00385333 -
Metabolic Mapping to Measure Retinal Metabolism
|
Phase 2 | |
Recruiting |
NCT04101604 -
Biomarkers of Common Eye Diseases
|
||
Completed |
NCT03702374 -
Combined Antioxidant Therapy on Oxidative Stress, Mitochondrial Dysfunction Markers in Diabetic Retinopathy
|
Phase 3 | |
Completed |
NCT01908816 -
An Open-label Extended Clinical Protocol of Ranibizumab to Evaluate Safety and Efficacy in Rare VEGF Driven Ocular Diseases.
|
Phase 3 | |
Completed |
NCT04009980 -
Long-term Retinal Changes After Topical Citicoline Administration in Patients With Mild Signs of Diabetic Retinopathy in Type 1 Diabetes Mellitus.
|
N/A | |
Completed |
NCT02924311 -
Routine Clinical Practice for Use of Intravitreal Aflibercept Treatment in Patients With Diabetic Macular Edema
|
||
Not yet recruiting |
NCT06257082 -
Video-based Patient Education Intervention for Diabetic Eye Screening in Latinx Communities
|
N/A | |
Not yet recruiting |
NCT05452993 -
Screening for Diabetic Retinopathy in Pharmacies With Artificial Intelligence Enhanced Retinophotography
|
N/A | |
Withdrawn |
NCT02812030 -
Aflibercept for Retinopathy in the Real World
|
N/A | |
Completed |
NCT02391558 -
Clinical Evaluation of Noninvasive OCT Angiography Using a Zeiss OCT Prototype to Compare to Fluorescein Angiography
|
N/A | |
Active, not recruiting |
NCT02330042 -
OCT Biomarkers for Diabetic Retinopathy
|
||
Active, not recruiting |
NCT02353923 -
OcuStem Nutritional Supplement in Diabetic Patients With Mild to Moderate Non-proliferative Retinopathy
|
N/A | |
Completed |
NCT02390245 -
Philadelphia Telemedicine Glaucoma Detection and Follow-Up Study
|
N/A |