Antivascular Endothelial Growth Factor Agents for Neovascular Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is the leading cause of severe visual loss and blindness over the age of 50 in developed countries. Vascular endothelial growth factor (VEGF) is considered as a critical molecule in the pathogenesis of choroidal neovascularization (CNV), which characterizes the neovascular AMD. Anti-VEGF agents are considered the most promising way of effectively inhibition of the neovascular AMD process. VEGF is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Two anti-VEGF agents have been approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. Pegaptanib sodium, which is an aptamer and ranibizumab, which is a monoclonal antibody fragment. Another humanized monoclonal antibody is currently off-label used, bevacizumab. This paper aims to discuss in details the effectiveness, the efficacy and safety of these three anti-VEGF agents. New anti-VEGF compounds which are recently investigated for their clinical usage (VEGF-trap, small interfering RNA) are also discussed for their promising outcomes

Evaluation of growth factors in vitreous and in serum in patients with non-proliferative and with proliferative diabetic retinopathy

Purpose: To measure the vitreous and serum levels of VEGF and PDGF isoforms (PDGF-AA, -AB, -BB) in PDR and NPDR patients and to investigate possible correlations between vitreous and/or serum levels of growth factors with parameters associated with PDR, or NPDR. Design: Case-controlled study. Participants: Thirty-one patients with PDR, fifteen patients with NPDR and fifteen non-diabetic patients (control group) were included in the study. Methods: Vitreous and serum samples were obtained during vitrectomy. PDGF-AA, -AB and -BB, as well as VEGF, were measured by enzyme-linked immunosorbent assay. Results: VEGF and all PDGF isoforms in vitreous were significantly increased in the PDR group, as compared to controls. Only VEGF in the vitreous correlated significantly to the activity of PDR. VEGF, PDGF-AA and -BB in vitreous correlated significantly to the severity of PDR. The levels of VEGF, PDGF-AB and -BB decreased significantly as the extent of PRP increased. Only VEGF vitreous levels correlated significantly to FNVD/E, but there were no 174 correlation between VEGF and/or PDGF isoforms vitreous levels and correlation between VEGF and/or PDGF isoforms vitreous levels and VH, TRD, PVD or HbAlC. There was no correlation between vitreous and serum levels of VEGF or PDGF isoforms in patients with PDR. Finally, there was significant correlation between the levels VEGF or PDGF isoforms in vitreous when compared in pairs. VEGF, PDGF-AA and -AB in vitreous was significantly higher in NPDR patients with CSME as compared to controls, while the concentration of PDGF-BB in vitreous was significantly lower in NPDR group with CSME than that in controls. VEGF and PDGF-AA vitreous levels correlated significantly to the severity of NPDR. There was no correlation between vitreous levels of VEGF or PDGF isoforms and extent of PRP, or HbAlC levels in serum. There was no correlation between vitreous and serum levels of VEGF or PDGF isoforms in patients with NPDR. Only vitreous concentrations of PDGF-AB correlated significantly to vitreous concentrations of PDGF-BB in NPDR group. The levels of VEGF, PDGF-AA, -AB and -BB in vitreous were significantly increased in the PDR group as compared to the NPDR group with CSME. There were no differences in levels of growth factors in serum between the three groups of patients. Conclusions: It appears that in addition to VEGF, PDGF-AA, -AB and -BB in the vitreous are also correlated with DR.Σκοπός: Ο προσδιορισμός της συγκέντρωσης στο υαλοειδές και στον ορό του VEGF και των ισομερών του PDGF (PDGF-AA, -AB, - ΒΒ) σε ΠΔΑ και σε ΜΠΔΑ και η συσχέτισή τους με παραμέτρους της ΠΔΑ και της ΜΠΔΑ. Υλικό και Μέθοδος: Στη μελέτη συμπεριλήφθηκαν 31 ασθενείς με ΠΔΑ, 15 ασθενείς με ΜΠΔΑ και 15 μη-διαβητικοί ασθενείς (ομάδα ελέγχου). Όλοι οι ασθενείς υποβλήθηκαν σε υαλοειδεκτομή κατά την οποία λήφθηκαν τα δείγματα υαλοειδούς. Τα δείγματα ορού λήφθηκαν αμέσως πριν την υαλοειδεκτομή. Ο προσδιορισμός του VEGF, του PDGF-AA, -AB και -ΒΒ στα δείγματα υαλοειδούς και ορού έγινε με την ανοσοενζυμική μέθοδο ELISA. Αποτελέσματα: Η συγκέντρωση του VEGF, του PDGF-AA, -AB και - ΒΒ στο υαλοειδές βρέθηκε σημαντικά υψηλότερη στην ομάδα με ΠΔΑ συγκριτικά με την ομάδα ελέγχου. Μόνο η συγκέντρωση του VEGF στο υαλοειδές συσχετίζεται σημαντικά με την ενεργότητα της ΠΔΑ. Η συγκέντρωση του VEGF, του PDGF-AA και -ΒΒ στο υαλοειδές συσχετίζεται σημαντικά με τη σοβαρότητα της ΠΔΑ. Ακόμη, βρέθηκε ότι η συγκέντρωση του VEGF, του PDGF-AB και - ΒΒ στο υαλοειδές μειώνεται σημαντικά όσο αυξάνεται η έκταση της ΠΑΦ. Μόνο η συγκέντρωση του VEGF στο υαλοειδές συσχετίζεται σημαντικά με την ύπαρξη ΙΝΔ/Α, ενώ δε βρέθηκαν συσχετίσεις μεταξύ της συγκέντρωσης των αυξητικών παραγόντων στο υαλοειδές και της ύπαρξης ΕΑ, ΕΑΑ, ΟΑΥ ή της συγκέντρωσης της HbA1C στον ορό. Ακόμη, δε βρέθηκε συσχέτιση μεταξύ της συγκέντρωσης των αυξητικών παραγόντων στο υαλοειδές και στον ορό, ενώ βρέθηκε ισχυρή συσχέτιση μεταξύ της συγκέντρωσης του VEGF στο υαλοειδές και όλων των PDGF ισομερών, όπως επίσης και μεταξύ της συγκέντρωσης των ισομερών του PDGF στο υαλοειδές ανά ζεύγη στους ασθενείς με Π.Δ.Α. H συγκέντρωση του VEGF, του PDGFΑΑ, και -AB στο υαλοειδές βρέθηκε σημαντικά υψηλότερη στην ομάδα με ΜΠΔΑ και με ΚΣΟΩ συγκριτικά με την ομάδα ελέγχου, ενώ η συγκέντρωση του PDGF-BB στο υαλοειδές βρέθηκε σημαντικά χαμηλότερη στην ομάδα με ΜΠΔΑ συγκριτικά με την ομάδα ελέγχου. Η συγκέντρωση του VEGF και του PDGF-AA στο υαλοειδές βρέθηκε ότι συσχετίζεται σημαντικά με τη σοβαρότητα της ΜΠΔΑ. Δε βρέθηκε συσχέτιση μεταξύ της συγκέντρωσης των αυξητικών παραγόντων στο υαλοειδές και της έκτασης της ΠΑΦ, ή της συγκέντρωσης της HbAlC στον ορό, δε βρέθηκε συσχέτιση μεταξύ της συγκέντρωσης των αυξητικών παραγόντων στο υαλοειδές και στον ορό, ενώ βρέθηκε ισχυρή συσχέτιση μόνο μεταξύ της συγκέντρωσης του PDGF-AB και του PDGF-BB στο υαλοειδές σε Μ.Π.Δ.Α. Η συγκέντρωση του VEGF, του PDGF-AA, -AB και -ΒΒ στο υαλοειδές βρέθηκε σημαντικά αυξημένη στην ομάδα της Π.Δ.Α. συγκριτικά με την ομάδα της ΜΠΔΑ. Δεν βρέθηκαν διαφορές στη συγκέντρωση των αυξητικών παραγόντων στον ορό μεταξύ των τριών ομάδων ασθενών. Συμπεράσματα: Εκτός από τον VEGF, και τα ισομερή του PDGF συσχετίζονται με το παθογενετικό υπόστρωμα της ΔΑ

Diabetic Retinopathy Treated with Laser Photocoagulation and the Indirect Effect on Glycaemic Control

Purpose. To identify any possible relation between glycaemic control and previous laser photocoagulation for diabetic retinopathy. Methods. Seventy-two patients with diabetes were included in the study and were separated into 2 groups according to previous treatment (group A) or not (group B) with argon laser photocoagulation. Glycaemic control was estimated by measuring blood levels of HbA1c in four consecutive measurements. Results. Blood levels of HbA1c in group A were significantly lower 3, 6, and 12 months after laser treatment as compared to blood levels of HbA1c before laser treatment (7.1±0.4% versus 7.6±0.9%, 7.2±0.2% versus 7.6±0.9%, and 7.1±0.2% versus 7.6±0.9%, resp., all P<0.05). Blood levels of HbA1c in group B did not differ significantly in four consecutive measurements. Conclusion. Our results suggest that we should anticipate a better glycaemic control in cases of patients with diabetes previously treated with laser photocoagulation

Clinical Study Diabetic Retinopathy Treated with Laser Photocoagulation and the Indirect Effect on Glycaemic Control

. Purpose. To identify any possible relation between glycaemic control and previous laser photocoagulation for diabetic retinopathy. Methods. Seventy-two patients with diabetes were included in the study and were separated into 2 groups according to previous treatment (group A) or not (group B) with argon laser photocoagulation. Glycaemic control was estimated by measuring blood levels of HbA1c in four consecutive measurements. Results. Blood levels of HbA1c in group A were significantly lower 3, 6, and 12 months after laser treatment as compared to blood levels of HbA1c before laser treatment (7.1 ± 0.4% versus 7.6 ± 0.9%, 7.2 ± 0.2% versus 7.6 ± 0.9%, and 7.1 ± 0.2% versus 7.6 ± 0.9%, resp., all &lt; 0.05). Blood levels of HbA1c in group B did not differ significantly in four consecutive measurements. Conclusion. Our results suggest that we should anticipate a better glycaemic control in cases of patients with diabetes previously treated with laser photocoagulation

Retinal and vitreous metastases from hepatocholangiocarcinoma.

BACKGROUND To report a case of metastatic hepatocholangiocarcinoma to the vitreous and retina. CASE PRESENTATION A 70-year-old male, who was recently diagnosed with hepatocholangiocarcinoma, was complaining of floaters in his right eye over the past 5 months and was referred to the Liverpool Ocular Oncology Centre. On presentation, his visual acuity in the right eye was 6/24. Fundus exam revealed a whitish, unilateral, full-thickness retinal lesion at the inferotemporal arcade of his right eye, with vitreous infiltration and subretinal fluid. The patient underwent 25G pars plana vitrectomy with biopsy, resection of the lesion and intravitreal bevacizumab injection. Histopathology testing of the surgical specimens confirmed the diagnosis of metastatic carcinoma to the eye. Two months postoperatively his visual acuity had improved to 6/7.5 and there was no sign of active disease in his right eye, while 9 months postoperatively his visual acuity decreased to 6/9.5 due to developing nuclear sclerotic cataract in his right eye. CONCLUSION The current report presents the first case of a hepatocholangiocarcinoma metastasis to the vitreous and retina