Vitreous Levels of Cysteine-rich 61 in Patients With Proliferative Diabetic Retinopathy (VL)

To determine the vitreous levels of fractalkine, cysteine-rich 61 (Cyr61), and VEGF in patients with PDR. Verifying that it is greater to that found in non-diabetic patients with different non-angiogenetic diseases.

Introduction: Angiogenesis, the growth and proliferation of new blood vessels, is an important aspect of the vascular proliferation found in tumor growth, wound repair, inflammatory states, and ischemic sequel in the ocular angiogenetic diseases. Intraocular neovascularization, the major eventually complication of diabetic mellitus, may result in vitreous hemorrhage, tractional retinal detachment, neovascularization glaucoma and eventually blindness. The involved factors include basic fibroblast growth factor (bFGF), insulin-like growth factor-I (IGF-I), vascular endothelial cell growth factor (VEGF), and Connective tissue growth factor (CTGF)/Cysteine-rich protein (Cyr61)/Nephroblastoma overexpressed gene (CCN) family. VEGF is a primary angiogenic factor that mediates ischemic-induced retinal neovascularization. VEGF level are elevated in the vitreous fluid in patients with proliferative diabetic retinopathy (PDR). The unselective anti-VEGF antibody bevacizumab has been used for the treatment of diabetic retinopathy. Problem: In spite of its potent anti-VEGF property, it does not completely inhibit ischemia-induced retinal neovascularization. Several other factors which were detected to have increased vitreous levels in the PDR patients might participate in the angiogenic process of diabetic retinopathy. One of the member of the CCN family, connective tissue growth factor (CTGF), was found to be involved in the angiogenesis and fibrosis mechanism of PDR. It is unclear if the other factors in the CCN family might also control the development of retinal angiogenesis and fibrosis.We measured vitreous cysteine-rich 61 (Cyr61) levels in PDR patients, non-diabetic patients,and PDR patients pretreated with bevacizumab. We further correlated the cysteine-rich 61 levels with different stages of PDR. Concomitant VEGF level was also measured to better understand the interaction of different factors.

Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 7 to 9 days before vitrectomy due to diabetic retinopathy.

Patients will receive intravitreal injection of 1.25 mg of bevacizumab (0.05 ml) 7 to 9 days before vitrectomy

Inclusion Criteria: Age ≥ 18 years Patients with type 1 or type 2 diabetes mellitus Not eligible for any currently approved treatments or experimental protocols Patients with PDR who receiving vitreoretinal surgery. Exclusion Criteria: A condition that would preclude a patient for participation in the study in opinion of investigator, e.g., unstable medical status including glycemic control and blood pressure Panretinal laser photocoagulation in the study eye Previous treatment with intravitreal or sub-Tenon triamcinolone History of submacular surgery or other surgical intervention for diabetic

Watanabe D, Suzuma K, Matsui S, Kurimoto M, Kiryu J, Kita M, Suzuma I, Ohashi H, Ojima T, Murakami T, Kobayashi T, Masuda S, Nagao M, Yoshimura N, Takagi H. Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy. N Engl J Med. 2005 Aug 25;353(8):782-92. doi: 10.1056/NEJMoa041773.