Endogenous VEGF Is Required for Visual Function: Evidence for a Survival Role on Müller Cells and Photoreceptors

Vascular endothelial growth factor (VEGF) is well known for its role in normal and pathologic neovascularization. However, a growing body of evidence indicates that VEGF also acts on non-vascular cells, both developmentally as well as in the adult. In light of the widespread use of systemic and intraocular anti-VEGF therapies for the treatment of angiogenesis associated with tumor growth and wet macular degeneration, systematic investigation of the role of VEGF in the adult retina is critical.Using immunohistochemistry and Lac-Z reporter mouse lines, we report that VEGF is produced by various cells in the adult mouse retina and that VEGFR2, the primary signaling receptor, is also widely expressed, with strong expression by Müller cells and photoreceptors. Systemic neutralization of VEGF was accomplished in mice by adenoviral expression of sFlt1. After 14 days of VEGF neutralization, there was no effect on the inner and outer retina vasculature, but a significant increase in apoptosis of cells in the inner and outer nuclear layers. By four weeks, the increase in neural cell death was associated with reduced thickness of the inner and outer nuclear layers and a decline in retinal function as measured by electroretinograms. siRNA-based suppression of VEGF expression in a Müller cell line in vitro supports the existence of an autocrine role for VEGF in Müller cell survival. Similarly, the addition of exogenous VEGF to freshly isolated photoreceptor cells and outer-nuclear-layer explants demonstrated VEGF to be highly neuroprotective.These results indicate an important role for endogenous VEGF in the maintenance and function of adult retina neuronal cells and indicate that anti-VEGF therapies should be administered with caution

Branch Retinal Vein Occlusion: Pathogenesis, Visual Prognosis, and Treatment Modalities

In branch retinal vein occlusion (BRVO), abnormal arteriovenous crossing with vein compression, degenerative changes of the vessel wall and abnormal hematological factors constitute the primary mechanism of vessel occlusion. In general, BRVO has a good prognosis: 50–60% of eyes are reported to have a final visual acuity (VA) of 20/40 or better even without treatment. One important prognostic factor for final VA appears to be the initial VA. Grid laser photocoagulation is an established treatment for macular edema in a particular group of patients with BRVO, while promising results for this condition are shown by intravitreal application of steroids or new vascular endothelial growth factor inhibitors. Vitrectomy with or without arteriovenous sheathotomy combined with removal of the internal limiting membrane may improve vision in eyes with macular edema which are unresponsive to or ineligible for laser treatment

INRAVITREAL BEVACIZUMAB COMBINED WITH CATARACT SURGERY FOR TREATMENT OF EXUDATIVE MACULAR DEGENERATION

PURPOSE: The aim of this study was to report on the combination of an intravitreal injection of bevacizumab and cataract surgery in patients with exudative age-related macular degeneration (AMD). METHODS: The interventional case series study included 11 patients (11 eyes) who received an intravitreal injection of 1.5 mg bevacizumab as treatment of exudative AMD (n = 10) or exudative myopic macular degeneration (n = 1), combined with a routine phacoemulsification and posterior chamber lens implantation for treatment of cataract. RESULTS: Intraoperatively and during the follow-up of 150 +/- 77.5 days, there were no complications related to the intravitreal application of bevacizumab combined with cataract surgery, such as wound dehiscence and leakage, delayed wound healing, corneal edema, dislocation of the pseudophakos, rupture of the posterior lens capsule, or rhegmatogenous retinal detachment. CONCLUSIONS: The results of this pilot study suggest that from a safety point of view, intravitreal injections of bevacizumab may be combined with routine cataract surgery

Effect of triamcinolone acetonide on proliferation of retinal endothelial cells in vitro and in vivo

Aim: To assess the effect of crystalline triamcinolone acetonide on retinal endothelial cell proliferation in vivo and in vitro. Methods: For in vitro analysis, a sprouting assay was employed. Bovine retinal endothelial cells were stimulated with basic fibroblast growth factor (bFGF) and incubated with different concentrations of triamcinolone acetonide (0.05 mg/ml to 8 mg/ml). For in vivo analysis, a retinopathy of prematurity (ROP) model was used. 16 C57BL/J6 mice were exposed to 75% oxygen from postnatal day 7 to day 12. On day 12, triamcinolone acetonide was intravitreally injected into one eye (“study eye”) and isotonic saline into the contralateral eye (“control eye”). On day 17, the mice were sacrificed and the eyes removed for quantitative analysis of preretinal neovascularisation. Four non-exposed mice served as negative control. Results: The sprouting assay demonstrated a dose dependent inhibition of bovine retinal endothelial cell proliferation from 0.05 mg triamcinolone acetonide/ml (no inhibition) to 3 mg triamcinolone acetonide/ml (complete inhibition). Dosages of more than 2 mg/ml resulted in cytotoxic changes of endothelial cells. The ROP model demonstrated a significantly lower neovascular cell count of 58% in the study group compared to the control group (6.35 (SD 2.1) cells per histological section versus 14.9 (SD 5.3) cells; p<0.005). Conclusions: Triamcinolone acetonide inhibits bFGF induced proliferation of retinal endothelial cells in vivo and in vitro. These findings contribute to understanding the mode of action and effects of triamcinolone acetonide on retinal neovascularisation

COMBINED INTRAVITREAL BEVACIZUMAB AND TRIAMCINOLONE IN EXUDATIVE AGE-RELATED MACULAR DEGENERATION

ABSTRACT. Purpose: We report on thè combined application of intravitreal bevacizumab and triamcinolone acetonide for treatment of exudative age-related macular degeneration (AMD). Methods: The clinical interventional case-series study included 16 patients (16 eyes) with exudative AMD who had previously received 3.5 ±1. 8 mono-injec-tions of bevacizumab (1.5 mg) without significant improvement in visual acuity (VA) or reduction in macular exudation. AH patients underwent a combined intravitreal injection of bevacizumab (1.5 mg) and triamcinolone acetonide (about 20 mg). Main outcome measures were VA and macular thickness as determined by optical coherence tomography. AH patients were re-examined at 2-3 months after thè intervention. Results: Visual acuity improved significantly (p = 0.03) from 0.80 ± 0.40 logMAR prior to thè combined injection to 0.65 ± 0.42 logMAR at 3 months after thè injection. An improvement of > 1 Snellen line was found in eight sub-jects, an increase of > 2 lines in five subjects, and an improvement of > 3 lines in two subjects. One patient lost 1 line and one patient lost 3 lines. Central retinal thickness decreased significantly from 272 ± 62 ^m to 220 ± 47 firn (p = 0.03). At thè 6-month follow-up examination, centrai retinal thickness had increased again to 319 ± 142 fan, which was not significantly (p = 0.30) different from baseline measurements. Conclusions: The combined intravitreal application of bevacizumab and triam-cinolone may temporarily be helpful in thè treatment of exudative AMD if previous intravitreal bevacizumab mono-injections bave failed to improve vision and reduce macular oedema

Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema

Aim: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. Methods: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3–12 months). Main outcome measures were visual acuity and intraocular pressure. Results: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). Conclusions: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used

VISUAL ACUITY CHANGE AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULARE DEGENERATION IN RELATION TO SUBFOVEAL MEMBRANE TYPE

PURPOSE: To examine an association between the subfoveal neovascular membrane type and visual acuity change after intravitreal bevacizumab injection for exudative age-related macular degeneration (AMD). METHODS: We carried out a clinical, retrospective, interventional case-series study including 66 consecutive patients (67 eyes) with exudative AMD who received an intravitreal injection of 1.5 mg bevacizumab. Study subgroups included the occult type without or with minimally classic subfoveal neovascularization (n = 28 eyes, 42%), predominantly or purely classic subfoveal neovascularization (n = 22 eyes, 33%), and eyes with retinal pigment epithelium detachment (n = 17 eyes, 25%). Follow-up was >or= 2 months. RESULTS: The maximal visual acuity (VA) gain (mean +/- standard deviation - 0.07 +/- 0.30 logMAR, 0.5 +/- 2.9 Snellen lines; p = 0.87), and VA gain at 1 month (p = 0.10), 2 months (p = 0.77) and 3 months (p = 0.35) after the injection did not vary significantly between the three study subgroups. Correspondingly, a multivariate analysis did not reveal a statistically significant (p = 0.57) influence of subfoveal lesion type on gain in VA. CONCLUSIONS: Visual improvement after intravitreal bevacizumab does not differ markedly between various types of subfoveal neovascularization in AMD