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• W1998163381 abstract "The unselective anti–vascular endothelial growth factor (VEGF) antibody bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) has been used for the treatment of diabetic retinopathy (DR), with early promising results.1Haritoglou C. Kook D. Neubauer A. et al.Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema.Retina. 2006; 26: 999-1005Crossref PubMed Scopus (375) Google Scholar, 2Avery R.L. Pearlman J. Pieramici D.J. et al.Intravitreal bevacizumab (Avastin) in the treatment of proliferative diabetic retinopathy.Ophthalmology. 2006; 113 (e6): 1695-1705Abstract Full Text Full Text PDF PubMed Scopus (707) Google Scholar However, little is known about its effect on retinal ischemia, which is a major factor in the pathogenesis and progression of DR. We therefore investigated the longitudinal changes in central and peripheral ischemia after intravitreal bevacizumab treatment by means of fluorescein angiography using a novel high-resolution ultrawide-field scanning laser ophthalmoscopy system. Consecutive patients who underwent intravitreal bevacuzimab at the Department of Ophthalmology, Ludwig-Maximilians University in Munich were evaluated. All had diffuse clinically significant macular edema and nonproliferative DR, had not responded to photocoagulation, and had not received any previous posterior segment surgery. All patients underwent ultrawide-field fluorescein scanning laser ophthalmoscopy angiography (Optomap 200 fa, Optos, Dunfermline, United Kingdom) and optical coherence tomography (Carl Zeiss Meditec, Jena, Germany) before and 4 weeks after the intravitreal injection of 1.25 mg of bevacizumab, as described previously.1Haritoglou C. Kook D. Neubauer A. et al.Intravitreal bevacizumab (Avastin) therapy for persistent diffuse diabetic macular edema.Retina. 2006; 26: 999-1005Crossref PubMed Scopus (375) Google Scholar Details of the scanning laser ophthalmoscopy fluorescein angiography examination technique have been described elsewhere.3Manivannan A. Plskova J. Farrow A. et al.Ultra-wide-field fluorescein angiography of the ocular fundus.Am J Ophthalmol. 2005; 140: 525-527Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar In brief, a series of digital images was taken after the rapid intravenous injection of 5 ml of a 10% solution of fluorescein. Each image covers an area of approximately 180° on the retina with an optical resolution of 3900×3072 pixels for that angle. This results in approximately 17 to 22 pixels per degree, yielding excellent imaging characteristics of both the retinal center and the periphery. The nonconfocal setup of the machine ensures simultaneous focus of all imaged structures. We assessed 2 pictures per patient eye at baseline and 2 at the 1-month follow-up: one from the early phase (<60 seconds) and one from the late arteriovenous phase (approximately 5 minutes). To assess central ischemia, caliper measurements of the width of the foveal avascular zone were performed. For grading peripheral retinal ischemia, we applied a special grid scheme (Fig 1 [available at http://aaojournal.org]) to the normalized images: the central field was placed in the macula’s center, the diameter of 1 field adjusted to match 1 disc diameter. Peripheral retinal ischemia was quantified by counting the number of fields out of the central 48 fields of the grid that were affected by significant ischemia (>50% of the field). Nonperfusion in terms of capillary dropout was defined analogous to literature reports.4Takahashi K. Kishi S. Muraoka K. Shimizu K. Reperfusion of occluded capillary beds in diabetic retinopathy.Am J Ophthalmol. 1998; 126: 791-797Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar All measurements were performed by one experienced investigator (LC) in arbitrary sequence who was masked to the clinical data and measurements. In 19 individuals, mean visual acuity (VA) before intravitreal bevacizumab was 0.87±0.37 logarithm of the minimum angle of resolution (logMAR) (i.e., 20/145). After 1 month, there was some improvement, of 0.13±0.28 logMAR (P = 0.08). Central macular thickness on optical coherence tomography was 440±146 μm, the foveal avascular zone diameter was 655±192 μm before therapy, and neither thickness nor diameter changed 4 weeks after therapy. Mean peripheral retinal ischemia decreased significantly, from 10.8±9.4 fields to 7.8±5.6 fields (P = 0.02), 1 month after intravitreal injection when assessed on early phase fluorescein angiography images. On late-phase images, the decrease was even more pronounced, from 14.8±10.5 to 8.6±6.3 fields (P<0.001). Some examples of typical changes are illustrated in Figure 2 (available at http://aaojournal.org). There was no correlation of peripheral ischemia to VA, optical coherence tomography thickness, or foveal avascular zone size. In summary, we could show semiquantitatively in a small series of patients with DR that intravitreal unselective anti-VEGF treatment improved peripheral ischemia in the short term. We saw no evidence of increasing ischemia, as might be feared in view of the systemic anti-VEGF side effects such as thrombembolism.5Ziemssen F. Bartz-Schmidt K.U. Grisanti S. (Side) effects of VEGF inhibition.Ophthalmologe. 2006; 103 ([in German]): 484-492Crossref PubMed Scopus (21) Google Scholar Limitations of the study include the small number of patients and short follow-up after only one administration. Although spontaneous improvements of capillary perfusion have been described in DR,4Takahashi K. Kishi S. Muraoka K. Shimizu K. Reperfusion of occluded capillary beds in diabetic retinopathy.Am J Ophthalmol. 1998; 126: 791-797Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar those appear to be associated with changes in metabolic control—absent, as far as we are aware, from our study. On the other hand, they may occur—over a significantly longer time—mostly with a pattern of intraretinal neovascularization,4Takahashi K. Kishi S. Muraoka K. Shimizu K. Reperfusion of occluded capillary beds in diabetic retinopathy.Am J Ophthalmol. 1998; 126: 791-797Abstract Full Text Full Text PDF PubMed Scopus (48) Google Scholar which was never observed in our series. In summary, the observed reduction of ischemia makes anti-VEGF therapy a promising approach in the treatment of DR, but further investigations with longer follow-up times are needed." @default.
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• W1998163381 title "Bevacizumab and Retinal Ischemia" @default.
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• W1998163381 doi "https://doi.org/10.1016/j.ophtha.2007.05.057" @default.
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