Subject(s)
Angioid Streaks/diagnosis , Bruch Membrane/pathology , Choroidal Neovascularization/diagnosis , Angioid Streaks/metabolism , Angioid Streaks/surgery , Basic Helix-Loop-Helix Transcription Factors/metabolism , Bruch Membrane/metabolism , Calcium/metabolism , Choroidal Neovascularization/metabolism , Choroidal Neovascularization/surgery , Fluorescein Angiography , Humans , Immunoenzyme Techniques , Male , Matrix Metalloproteinase 9/metabolism , Middle Aged , Vascular Endothelial Growth Factor A/metabolism , VitrectomyABSTRACT
PURPOSE: To investigate the vitreous levels of bevacizumab and vascular endothelial growth factor-A (VEGF-A) after intravitreal injection of the drug in patients with choroidal neovascularization (CNV). DESIGN: Interventional case series. PARTICIPANTS: Eleven eyes of 11 patients with submacular hemorrhage and CNV due to age-related macular degeneration (n = 10) or angioid streaks (n = 1). METHODS: All patients were treatment naïve except for a single dose of intravitreal injection of bevacizumab (1.25 mg/50 muL dose) and subsequent vitrectomy after various intervals (1-101 days) because of active and progressive lesion. Intravitreal free bevacizumab and VEGF-A levels were measured using enzyme-linked immunosorbent assay and microsphere-based immunoassay, respectively. Vitreous VEGF-A isoforms were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. MAIN OUTCOME MEASURES: Intravitreal bevacizumab and VEGF-A levels were measured and pharmacokinetic parameters were calculated. RESULTS: Pharmacokinetics of intravitreal bevacizumab followed a 2-compartment model with initial and terminal half-lives of 0.5 and 6.7 days, respectively. Bevacizumab could be detected in all cases, ranging from 2.63 ng/ml to 165 microg/ml. The peak concentration was observed on the second day after intravitreal bevacizumab injection. Vitreous free VEGF-A levels ranged from 0.2 to 33.9 pg/ml and showed a negative correlation with the bevacizumab concentration (P<0.001; r = -0.955) and a positive correlation with time (P<0.001; r = 0.964). However, the percentage expression of VEGF-A(165) exhibited a positive correlation with the bevacizumab concentration (P = 0.032, r = 0.645) and a negative correlation with time (P = 0.007, r = -0.755). A time-dependent increase was found for the percentage expression of VEGF-A(189) (P = 0.023, r = 0.673). Neither bevacizumab- nor time-related alterations were found for VEGF-A(121). CONCLUSIONS: Based on pharmacokinetics, the interval of 6-7 weeks would be appropriate for efficacy, although clinical trials should guide dosing recommendations. Vitreous levels of free VEGF-A showed a negative correlation with the bevacizumab concentration, which confirmed the in vivo binding affinity of bevacizumab to VEGF-A. The analysis of the VEGF-A isoforms suggests differences of interaction between bevacizumab and individual VEGF-A isoforms.
Subject(s)
Angiogenesis Inhibitors/pharmacokinetics , Antibodies, Monoclonal/pharmacokinetics , Choroidal Neovascularization/metabolism , Vascular Endothelial Growth Factor A/pharmacokinetics , Vitreous Body/metabolism , Aged , Aged, 80 and over , Angioid Streaks/complications , Angioid Streaks/metabolism , Antibodies, Monoclonal, Humanized , Bevacizumab , Blotting, Western , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/etiology , Electrophoresis, Polyacrylamide Gel , Enzyme-Linked Immunosorbent Assay , Female , Half-Life , Humans , Injections , Macular Degeneration/complications , Macular Degeneration/metabolism , Male , Middle Aged , Retinal Hemorrhage/etiology , Retinal Hemorrhage/metabolism , VitrectomyABSTRACT
The clinical study presents the association between optic disc drusen and angioid streaks in the context of pseudoxanthoma elasticum, in 8.5% (4 from 47) of the cases. The values are significantly higher compared to those from the normal population (0.34%). This result can be the consequence of pathogenic correlations between the two diseases, in which a role is attributed to the metabolic changes within the pseudoxanthoma elasticum. The starting point seems to be the accumulation of polyanions in the elastin of the cribriform plate, followed by disruption of axonal transport, mitochondrial extrusion and subsequent formation of optic disc drusen.
Subject(s)
Angioid Streaks/pathology , Optic Disk Drusen/pathology , Pseudoxanthoma Elasticum/pathology , Adult , Aged , Angioid Streaks/diagnosis , Angioid Streaks/metabolism , Diagnosis, Differential , Female , Fluorescein Angiography , Fundus Oculi , Humans , Male , Middle Aged , Optic Disk Drusen/diagnosis , Optic Disk Drusen/metabolism , Pseudoxanthoma Elasticum/diagnosis , Pseudoxanthoma Elasticum/genetics , Pseudoxanthoma Elasticum/metabolismSubject(s)
Angioid Streaks/metabolism , Endothelial Growth Factors/biosynthesis , Macular Degeneration/metabolism , Receptors, Vascular Endothelial Growth Factor/biosynthesis , Antigens, CD34/biosynthesis , Extracellular Matrix Proteins/metabolism , Humans , Immunohistochemistry , Neovascularization, Pathologic , Placenta Growth Factor , Pregnancy Proteins/metabolism , Vascular Endothelial Growth Factor A , Vascular Endothelial Growth Factor B , Vascular Endothelial Growth Factor C , Vascular Endothelial Growth Factor D , Vascular Endothelial Growth Factor Receptor-3/metabolismABSTRACT
In a case of pseudoxanthoma elasticum (PXE), Bruch's membrane was studied histochemically, ultrastructurally and by element analysis. Two kinds of calcifications were observed, one composed of hydroxyapatite and the other of CaHPO4. They were seen in the scar tissue of angioid streak areas and in the membrane outside these areas, respectively. Furthermore, a thready material was found in the membrane as well as an increased amount of acid mucopolysaccharides. The genesis of the calcifications and the pathogenesis of angioid streaks are discussed. The author is in favor of a malformed collagen as the basic defect in PXE.