OCT angiography in the diagnosis of neovascular types in age-related macular degeneration Irina Panova¹, MD, Timur Shaimov¹ ² Ruslan Shaimov², Venera Shaimova² 15th Euretina Congress Nice 2015 ¹Department of Ophthalmology, South Ural State Medical University ²“Vision” Eye Center, LLC Chelyabinsk, Russian Federation

Introduction Neovascular Age-related Macular Degeneration (nAMD) Cause of vision loss in patients over 60 years No rehabilitation in terminal stage of disease Low quality of life in patients with nAMD 10% in structure of AMD 3 types of neovascularization: Type I (occult CNV) – neovascularization under the retinal pigment epithelium (RPE) Type II (classic CNV) – neovascularization above the RPE Type III (retinal angiomatous proliferation) – intraretinal neovascularization with retinal and chorioretinal anastomosis The «Gold standard» of the CNV diagnostic – Fluorescein angiography (FA), but there are some disadvantages: Requires intravenous administration of dye Time-consuming (10-30 min) Allergic reactions and side effects are possible Two-dimensional image Frequent application is difficult Optical coherence tomography angiography (OCT-angiography, angio-OCT) – novel method of blood flow visualization in retina, optic nerve head (ONH) and choroid Non-invasive, dyeless and safe method – no allergic reactions and side effects Fast - six seconds to obtain an image Three-dimensional layer-by-layer scanning from internal limiting membrane (ILM) to the choroid Structural and functional (i.e. blood flow) information Purpose To identify OCT angiography opportunities in the diagnosis of neovascularization types in age-related macular degeneration. Blinder K.J., Bradley S., Bressler N.M. et al. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report one // Am. J. Ophthalmol.– 2003.– Vol. 136.– P. 407-418. Gass JD. Stereoscopic Atlas of Macular Diseases, Fourth Edition. St. Louis: C.V. Mosby; 1997:26–30. Jia Y, Bailey ST, Wilson DJ, Tan O, Klein ML, Flaxel CJ, et al. Quantitative Optical Coherence Tomography Angiography of Choroidal de Carlo et al. International Journal of Retina and Vitreous (2015) 1:5 Page 14 of 15 Neovascularization in Age-Related Macular Degeneration. Ophthalmology. 2014;121:1435– 44. Spaide RF, Klancnik JM, Cooney MJ. Retinal Vascular Layers Imaged by Fluorescein Angiography and Optical Coherence Tomography Angiography.JAMA Ophthalmol. 2014; E1-6. doi:10.1001/jamaophthalmol.2014.3616. Jia Y, Tan O, Tokayer J et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710. doi:10.1364/oe.20.004710.

Material & Methods Four layers may be evaluated with OCT angiography: We studied 28 patients (34 eyes) with neovascular AMD, undergoing ophthalmic examination in Eye Center “Vision” LLC and at the Department of Ophthalmology, SUSMU, Chelyabinsk, Russia. Men – 8, Women - 20. The mean age of the patients was 70,2 ± 7,6 years. All participants underwent standard ophthalmic examination, fluorescein angiography, OCT angiography on the Optovue RTVue XR Avanti (Optovue Inc, USA) device. The scanning speed during angiography OCT was 70,000 A-scans per second, with an average wavelength 840 nm. The movement of blood cells in the vessels was the cause of reflectivity changes (signal change - decorrelation) from the first to the second 3D scan of the points corresponding to the internal volume of the vessel. According to the results of OCT angiography were evaluated: layered localization, neovascular network area, texture and shape of newly formed blood vessels. Lesion area was calculated using the software Adobe Photoshop CS6 (Adobe Systems, Inc.). Four layers may be evaluated with OCT angiography: Superficial plexus Deep plexus Outer Retina Choroid Capillary No blood flow in normal retina

Results Type I CNV Type II CNV A B C D E A B C D E 76-years old man with neovascular AMD, type I neovascularization of right eye BCVA OD = 0,7 A) Color fundus photography. Yellowish area with pigment redistribution and retinal swelling B) FA, early phase – heterogeneous area of hyperfluorescence with unclear margins C) FA, late phase – pooling in neurosensory retinal detachment (NRD) area D) Structural OCT – NRD in fovea, RPE detachment juxtafoveally and parafoveally E) OCT angiography, 3x3mm (red dotted square on the image B, double red line on the image D shows the scan level) – a tree-like vascular network with large feeder vessel is located under the RPE. Neovascular network area = 3,02 mm² 63-years old woman with neovascular AMD, type II neovascularization of right eye BCVA OD = 1,0 A) Color fundus photography. Yellow-grayish lesion in nasal segment of macula with some subretinal hemorrhages B) FA, early phase – hyperfluorescent area with clear margins C) FA, late phase – leakage from classic neovascular membrane D) Structural OCT – hyperreflective area above the RPE in nasal segment of macula. Some intraretinal cystoid spaces juxtafoveally E) OCT angiography, 6x6mm (double red line on the image D shows the scan level) – dense vascular network with numerous loop-like vessels. Feeder vessel is growing from peripapillary area. Neovascular network area = 2,21 mm²

Results neovascular network changes during anti-VEGF therapy B C D BCVA OS = 0,2 BCVA OS = 0,4 E F G H 1 day before anti-VEGF 3 days after anti-VEGF 11 days after anti-VEGF 24 days after anti-VEGF S=0,73mm² S=0,23mm² S=0,00 mm² S=0,11 mm² S=1,91 mm² A C 1 day before anti-VEGF BCVA OS = 0,09 B D 30 days after anti-VEGF BCVA OS = 0,2 S=0,36 mm² 67 years-old man with neovascular AMD, type II CNV of the left eye. Received one intravitreal injection of Ranibizumab (IVR) Structural OCT images (A-D): Reducing of the height of hyperreflective area above the RPE Angio-OCT images (E-H): A tree-like neovascular membrane above the RPE (E); reducing of the dense of vascular network on 3rd day after IVR (F); no signs of neovascularization on 11th day after IVR (G); recurrence of neovascularization under RPE on 30th day after IVR (H) 88 years-old man with neovascular AMD, mixed CNV of the right eye. Received one intravitreal injection of Ranibizumab. Structural OCT images (A,B): Reducing of the height of hyperreflective area above RPE, full resorbtion of subretinal fluid (NRD) Angio-OCT images (C,D): A tree-like neovascular network under the RPE and dense neovascular membrane above the RPE (C); reducing of the dense of neovascular network above the RPE on the 30th day after IVR

Thank you for your attention! Conclusions OCT angiography allows to visualize blood flow in different types of neovascularization and to determine the vascular network area, which can help to evaluate the results of neovascular AMD treatment. Non-invasiveness of this method ensures the safety and the possibility of unlimited multiplicity of applications. Further studies are needed to evaluate sensitivity and specificity of OCT angiography in the diagnosis of vascular abnormalities in the human eye. Thank you for your attention!