Download Angiofibrotic Response to Vascular Endothelial Growth Factor

Angiofibrotic Response to Vascular
Endothelial Growth Factor Inhibition in
Diabetic Retinal Detachment: Report No. 1
Sohn EH, He S, Kim LA, et al. Angiofibrotic response to vascular
endothelial growth factor inhibition in diabetic retinal detachment.
Arch Ophthalmol. 2012;130(9):1127-1134.
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Introduction
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Factors responsible for traction retinal detachment (TRD) in proliferative
diabetic retinopathy (PDR) are unclear.
– Vascular endothelial growth factor (VEGF) drives neovascularization.
– Connective tissue growth factor (CTGF) is linked to fibrosis.
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Decreasing VEGF levels (with laser or intravitreal bevacizumab) can
accelerate fibrosis and TRD.
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Aims of this report:
(1) Describe study design and summarize patient baseline characteristics.
(2) Provide early clinical results.
(3) Report the effect of VEGF inhibition on VEGF and CTGF in ocular fluid.
(4) Examine the correlation of aqueous to vitreous levels of these growth
factors.
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Methods
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Prospective, randomized, double-masked, interventional study of eyes
needing vitrectomy for TRD due to PDR.
– Two study arms: intravitreal bevacizumab injection (1.25 mg) vs sham
injection (control).
– Vitrectomy was performed 3-7 days after injection.
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Preoperative and intraoperative assessments of fibrovascular membranes
were performed; intraoperative bleeding was recorded.
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Samples were extracted for laboratory analysis:
– Preinjection aqueous.
– Intraoperative aqueous, vitreous, and membranes.
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Methods
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Ocular fluid levels were analyzed by enzyme-linked immunosorbent assay:
– VEGF and CTGF.
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Statistical analysis of clinical data was performed.
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Limitations:
– Small sample size (20 eyes of 19 patients).
– Severe disease with predominantly fibrotic membranes.
– Fluid samples were extracted within 7 days after injection, which may be
too early to assess for an increase in fibrosis or an effect on growth
factors.
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Results
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15 of 20 enrolled eyes had severe TRD or TRD/rhegmatogenous retinal
detachment.
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5 eyes had clinically observable regression of neovascularization (all in the
treated group).
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Visual acuity changes from preoperatively  3 months postoperatively:
– Controls: 20/400  20/400.
– Treated: 8/200  20/100
– P = .30 between controls and treated at 3 months postoperatively.
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Vitreous: VEGF higher in controls than treated (P = .03); CTGF levels
unchanged between the 2 arms.
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Aqueous: VEGF and CTGF unchanged between the 2 arms.
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Results
Preoperative,
Intraoperative,
and POM3
Results With
Vitreous VEGF
and CTGF Levels
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Results
Correlation of aqueous levels of CGTF with vitreous levels of
CTGF. Spearman correlation coefficient of 0.95 indicates high
correlation (P < .001).
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Comment
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Vitreous (but not aqueous) VEGF levels are suppressed within 4 days after
intravitreal bevacizumab injection (1.25 mg).
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3-7 days after bevacizumab injection may be too early to see upregulation
of CTGF levels in the vitreous.
– Suggests scientific rationale for performing vitrectomy within 1 week of
preoperative intravitreal bevacizumab injection for eyes with TRD in
PDR.
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Aqueous CTGF level may be a useful surrogate for vitreous CTGF level in
this subset of eyes with severe PDR.
– Same cannot be said for VEGF.
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Comment
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CTGF is involved in intraocular fibrosis, but the precise relationship to
VEGF is still unclear.
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Analysis of membranes extracted from study eyes may provide more insight
into the mechanism of “angiofibrotic switch.”
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Detailed anatomic retinal analysis and long-term follow-up of clinical
outcomes will be presented in future reports.
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Contact Information
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If you have questions, please contact the corresponding author:
– Elliott H. Sohn, MD, Department of Ophthalmology, University of Iowa
Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA 52242
([email protected]).
Funding/Support
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This study was supported by the Eugene de Juan Jr Award for Innovation
(Dr Sohn), the Heed Foundation (Drs Kim and Javaheri), grant K12EY16335 from the National Eye Institute, National Institutes of Health (Dr
Kim), The Arnold and Mabel Beckman Foundation (Dr Hinton), Research to
Prevent Blindness (Department of Ophthalmology, University of Iowa
Hospitals and Clinics), and core grant EY03040 from the National Eye
Institute (Doheny Eye Institute).
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