Focal macular electroretinograms after intravitreal injections of bevacizumab for age-related macular degeneration.

PURPOSE: To evaluate the changes in the best-corrected visual acuity (BCVA), macular thickness, and focal macular electroretinograms (FMERGs) after three intravitreal injections of bevacizumab for a choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). METHODS: The medical records of 18 eyes of 18 patients who had received three consecutive monthly intravitreal injections of bevacizumab were retrospectively studied. The BCVA, macular thickness determined by optical coherence tomography (OCT), and FMERGs were measured before the first injection, and 10 days after each of the intravitreal bevacizumab injections. RESULTS: The number of eyes with improvement in BCVA after the first injection was one (6%), after the second injection was four (22%), and after the third injection was five (28%). The number of eyes with reduction in macular thickness was 4 (33%), 8 (44%), and 10 (56%) after each of the three injections. The number of eyes with increase in b-wave amplitude of the FMERGs was 7 (38%), 6 (33%), and 10 (56%) after each of the three each injections. The mean macular thickness was significantly thinner after the first injection, and the mean BCVA was significantly improved after the second injection. The mean amplitude and implicit time of the b-wave of the FMERGs were significantly improved only after the third injection (P<0.05). CONCLUSIONS: All parameters improved but the best was after the third injection, indicating that three monthly intravitreous injections with bevacizumab may be an effective treatment regimen for AMD.

Significant correlation between electroretinogram parameters and ocular vascular endothelial growth factor concentration in central retinal vein occlusion eyes.

PURPOSE: Central retinal vein occlusion (CRVO) leads to retinal ischemia, which then induces an upregulation of vascular endothelial growth factor (VEGF). The aim of this study was to determine whether a significant correlation exists between the ocular VEGF levels and the amplitudes and implicit times of different components of the electroretinogram (ERG) in eyes with a CRVO. METHODS: The medical records of the 20 consecutive patients who had macular edema secondary to CRVO and were examined at the Nagoya University Hospital from November 2008 to February 2010 were reviewed. Because all the patients were scheduled to receive an intravitreal injection of bevacizumab (IVB), it was possible to collect samples of the aqueous humor before the IVB. The correlation between the different components of the ERGs and the VEGF concentration in the aqueous was determined. RESULTS: The mean VEGF concentration of the aqueous humor was 416 pg/mL with a range of 100-1260 pg/mL. The b/a ratio of the single flash ERGs (P = 0.049; ρ = -0.45), implicit times of the cone a-wave (P = 0.028; ρ = 0.50), cone b-wave (P = 0.0059; ρ = 0.63), and 30 Hz flicker ERGs (P = 0.0058; ρ = 0.63) were significantly correlated with the VEGF concentration in the aqueous. CONCLUSIONS: The significant correlations between the different components of the ERGs and the aqueous VEGF concentration indicate that full-field ERGs can be used to detect the CRVO patients at a high risk of developing neovascularization of the iris.

Suppression of choroidal neovascularization and quantitative and qualitative inhibition of VEGF and CCL2 by heparin.

PURPOSE: To study the effect of heparin on the development of laser-induced choroidal neovascularization (CNV) and to assess the underlying molecular mechanisms. METHODS: Bone marrow transplantation (BMT) was conducted by intravenous injection of green fluorescence protein (GFP)-labeled bone marrow cells (1 × 10(7) cells) into irradiated (9 Gy) C57BL/6J mice. Laser photocoagulation was applied to induce CNV; subsequently, unfractionated heparin or phosphate-buffered saline was injected into mice that did or did not undergo BMT. The area of CNV, distribution of injected heparin, and quantities of infiltrating cells positive for Griffonia simplicifolia (GS) and GFP inside and outside the CNV were evaluated. Effects of heparin on the secretion of VEGF, CCL2, and TNF-α by ARPE19 cells and on the binding of VEGF, CCL2, TNF-α, and their receptors were analyzed in vitro. RESULTS: Intravitreal injection of heparin at higher doses reduced the size of the CNV. Heparin localized at the vascular structures and photoreceptor layers adjacent to the laser scar. Only GS-positive cells infiltrating outside the CNV were reduced significantly, but not those inside the CNV or those expressing GFP. Relative decreases in VEGF and CCL2 levels were observed in media of ARPE19 cells at higher heparin concentrations. In vitro binding assays revealed that heparin and porcine ocular fluid, respectively, suppressed the binding of VEGF to VEGFR2 and CCL2 to CCR2. CONCLUSIONS: Intravitreal heparin injection inhibited CNV development. Reduced VEGF and CCL2 secretion by RPE cells and suppression of VEGF-VEGFR2 and CCL2-CCR2 interactions at the laser site mediated by heparin may contribute to the pharmacologic effect.