ICG IMAGING FOR EXUDATIVE ARMD

Transcription

1 ICG IMAGING FOR EXUDATIVE ARMD MARK H. NELSON, MD MBA WINSTON-SALEM, NC ASRS INSTRUCTION COURSE AUGUST 24, 2011 FINANCIAL DISCLOSURE Novartis Pharmaceutics, Incorporated Consultant, Grant Recipient Heidelberg Engineering, Incorporated Consultant, Speaker QLT, Incorporated Consultant, Speaker Eyetech, Incorporated Consultant, Speaker ICG IMAGING FOR OVERVIEW Inflection point use of anti-vegf monotherapy Diagnostic Testing IVFA ANCHOR AND MARINA Time-domain OCT axial interpretation Spectral-domain OCT, ICG, multimodality imaging Strategy for treating Exudative ARMD TIME-DOMAIN OCT Time-domain OCT axial interpretation and quantification of pathology SPECTRAL- DOMAIN OCT Improved resolution, image capture sustaining innovation. ELM, IS/OS and interface, RPE, Bruch s Membrane, choroid ICG IMAGING FOR ICG Didn t we have ICG in early 2000? ICG indications strong recommendation (Stanga, P.E., et al. Ophthalmology, 2003) Occult Choroidal Vasculopathy Neovascularization associated with RPED Recurrent Neovascularization Polypoidal Vasculopathy Yannuzzi AJO, 2011 Cohen Retina, 2011 ICG IMAGING EQUIPMENT Spectral-Domain OCT Confocal scanning laser ophthalmoscopy High-speed images with excellent resolution and contrast Dual-beam simultaneous imaging Tru-track eye tracking 40,000 A-scans per second Resolution is a limitation microns for ICG however IVFA has resolution of vessels as small as 10 microns. MULTIMODALITY IMAGING Disruptive innovation in the diagnosis and treatment of Exudative ARMD. Six modalities: IVFA OCT ICG AUTOFLOURESCENCE INFRARED RED FREE IVFA VS. ICG IVFA water soluble prompt leakage vessels contrast with dark background of RPE 494 nm absorption/521 nm emission ICG (Indocyanine Green) protein bound large molecule metabolized by liver short half life 805 nm absorption/839 nm emission infrared transmits through mild heme and crosses normal macular pigments

2 MULTIMODALITY IMAGE CAPTURE IVFA/ICG MULTIMODALITY IMAGE CAPTURE IVFA/ICG MULTIMODALITY IMAGE CAPTURE IVFA/ICG MULTIMODALITY IMAGE CAPTURE IVFA/ICG MULTIMODALITY IMAGE CAPTURE IVFA/OCT MULTIMODALITY IMAGE CAPTURE IVFA/OCT ANDA NEED TWO EXAMPLES OF OCT/IVFA MULTIMODALITY IMAGE CAPTURE ICG/OCT MULTIMODALITY IMAGE CAPTURE ICG/OCT MULTIMODALITY IMAGE CAPTURE AF/OCT

3 MULTIMODALITY IMAGING ANTI-VEGF RESISTANT LESIONS ICG and multimodality imaging allows for identifying two specific lesions Neovascularization with arteriolarization Polypoidal vasculopathy MULTIMODALITY IMAGING ANTI-VEGF RESISTANT LESIONS MULTIMODALITY IMAGING ANTI-VEGF RESISTANT LESIONS CLASSIC ARTERIOLARIZED NEOVASCULARIZATION Classic neovascularization with arteriolarization MULTIMODALITY IMAGING ANTI-VEGF RESISTANT LESIONS OCCULT ARTERIOLARIZED NEOVASCULARIZATION Occult neovascularization with arteriolarization EXUDATIVE ARMD OCCULT MEMBRANE The word occult comes from the Latin word occultus (clandestine, hidden, secret), referring to "knowledge of the hidden" The term is sometimes popularly taken to mean "knowledge meant only for certain people" or "knowledge that must be kept hidden MULTIMODALITY IMAGING ANTI-VEGF RESISTANT LESIONS POLYPOIDAL VASCULOPATHY Differentiation between traditional Polypoidal Vasculopathy and Exudative ARMD/drusen and polyps OCT reveals localized, steeply sloped elevation of RPE. Need ICG to diagnose (at first) IVFA reveals non-specific neovascularization, i.e. occult EXUDATIVE ARMD DEFINITIONS Induction Maintenance Persistent Leakage Primary Anti-VEGF Failure Secondary Anti-VEGF Failure Anti-VEGF sensitive Anti-VEGF resistant Anti-VEGF dependent Exudative ARMD sub-classifications CREATING STRATEGY PERSISTENT LEAKAGE Dadgostar, H., et al. (2009) Cho, et al (2009) Schaal/Farooghian (2008/2009) CATT NEJM, May 2011 SUB -CLASSIFICATION Classic subretinal neovascularization Type II Without arteriolarized neovascularization With arteriolarized neovascularization Associated with occult membrane formation Associated with polypoidal vasculopathy Occult membrane formation Type I Associated with arteriolarized neovascularization Associated with polypoidal vasculopathy Retinal pigment epithelial detachment with arteriolarized neovascularization Retinal pigment epithelial detachment with polypoidal vasculopathy RAP lesion (Type III) Pseudovitelliform variants (Type IV)

4 SUB -CLASSIFICATION Goal of sub-classification Determine clinical response to specific sub-types Anti-VEGF resistant lesions Anti-VEGF Resistant Anti-VEGF Dependent Create phenotypes for genetic analysis Better understand pathophysiology Classic Neovascularization why does it occur? Polypoidal Vasculopathy what is it? SUB CLASSIFICATION CLASSIC NEOVASCULARIZATION Classic subretinal neovascularization Type II Without arteriolarized neovascularization With arteriolarized neovascularization SUB CLASSIFICATION CLASSIC NEOVASCULARIZATION Classic subretinal neovascularization Type II Associated with occult membrane formation Associated with polypoidal vasculopathy SUB CLASSIFICATION OCCULT MEMBRANE Occult membrane formation Type I Associated with arteriolarized neovascularization SUB CLASSIFICATION OCCULT MEMBRANE Occult membrane formation Type I Associated with polypoidal vasculopathy SUB CLASSIFICATION RPED/OCCULT MEMBRANE STRATEGY - SUB CLASSIFICATION RPED/OCCULT MEMBRANE STRATEGY - SUB CLASSIFICATION RPED/RAP LESION SUB CLASSIFICATION ATYPICAL PRESENTATION Atypical Vitelliform Lesions Freund, et al, Retina, 2011.

5 STRATEGY - DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1 - Does the patient have evidence of ARMD? Is there leakage? Where is the leakage? Is it from the ARMD (i.e. Exudative) or are there other concurrent processes? What are my goals for treatment? Complete leakage resolution is this critical? Optimal visual rehabilitation Decreased treatment burden matching resources with disease STRATEGY - DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Where is the leakage? Intraretinal Subretinal Sub-RPE Anda, need a picture showing all three -?Harry Underwood early on DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Does the patient have pathology that looks like Exudative ARMD?Pseudophakic CME? Macular pucker? DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Does the patient have pathology that looks like Exudative ARMD? Vasculopathy? STRATEGY - DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Does the patient have pathology that looks like Exudative ARMD? Arteriolar Macroaneurysm? Anda Mr. Hensdale IVFA/ICG and ICG/OCT or IVFA/OCT DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Does the patient have pathology that looks like Exudative ARMD? MacTel 2? DOES THE PATIENT HAVE EXUDATIVE ARMD? QUESTION #1: Does the patient have pathology that looks like Exudative ARMD? Central Serous Chorioretinopathy QUESTION #2 - If the patient has Exudative ARMD, do they have classic, occult, or both types of neovascularization? MULTIMODALITY IMAGING - CREATING STRATEGY OCCULT, CLASSIC, OR RAP? STRATEGY - OCCULT, CLASSIC, OR RAP? QUESTION #2 - If the patient has Exudative ARMD, what types are present can we determine the subclassification? ICG Videoangiography Presence of anti-vegf lesions: arteriolarized neovascularization and polypoidal vasculopathy RAP lesions Multimodality Imaging Sub-classification of Classic and Occult

6 STRATEGY - OCCULT, CLASSIC, OR RAP? QUESTION #3 - If there is an occult membrane, is there a network of arteriolarized neovascularization or polypoidal vasculopathy, i.e. components that are likely to make the patient anti-vegf resistant? MULTIMODALITY IMAGING - CREATING STRATEGY - OCCULT, CLASSIC OR RAP? QUESTION #4 - If it is classic membrane, are the vessels arteriolarized? Are they associated with occult membrane? Are they associated with polypoidal vasculopathy? MULTIMODALITY IMAGING - CREATING STRATEGY - OCCULT, CLASSIC OR RAP? QUESTION #5 Is there a RAP lesion? STRATEGY - OVERVIEW QUESTION #6 What is the strategy behind treating Exudative ARMD? 1. Determine pathology and sub-classification. 2. Study guidance? Induction and Maintenance ANCHOR and MARINA PrONTO LEVEL 3. Response to Induction and Maintenance Anti-VEGF Sensitive Anti-VEGF Resistant Anti-VEGF Dependent 4. Combination Therapy ICG-directed Triple Therapy with Visudyne/Lucentis/Triescence EXUDATIVE ARMD CLASSIC NEOVASCULARIZATION ANTI-VEGF SENSITIVE EXUDATIVE ARMD OCCULT AND CLASSIC NEOVASCULARIZATION ANTI-VEGF SENSITIVE STRATEGY - EXUDATIVE ARMD RAP LESION ANTI-VEGF SENSITIVE STRATEGY - EXUDATIVE ARMD CLASSIC NEOVASCULARIZATION ANTI-VEGF RESISTANT STRATEGY - EXUDATIVE ARMD CLASSIC NEOVASCULARIZATION ANTI-VEGF DEPENDENT

7 EXUDATIVE ARMD OCCULT NEOVASCULARIZATION ANTI-VEGF DEPENDENT THERAPY Rescue Protocol Treatment of anti-vegf resistant lesions, i.e. Primary Anti-VEGF Failures Treatment of anti-vegf dependent lesions i.e. Secondary Anti- VEGF Failures Primary Protocol THERAPY Equipment needed: Multimodality imaging utilizing ICG/IVFA/OCT PDT laser Staff willing to manage operational issues Rationale: existing vessels (PDT), inflammation (triamcinolone), new vessels/upregulation of VEGF (Lucentis) Method Day 0 Lucentis (0.5 mg) Day 3-14 ICG-Directed PDT Triple Therapy with Visudyne and Triamcinolone Acetonide (4mg) THERAPY THERAPY GROUP OCT (MICRONS) RESCUE (45) RPED (15) VISION (LETTERS) 5 (15% > 3 lines) (25% > 2 lines) ( 0% <3 lines) 4 (7%>3 lines) (21% >2 lines) (0% < 3 lines) PRIMARY (20) (29% > 3 lines) (59% >2 lines) (0% < 3 lines) DURATION (WEEKS) (19.7 POLYP) (48.7 ART. NV) THERAPY CASE REPORTS STRATEGY - EXUDATIVE ARMD ICG-DIRECTED PDT TRIPLE THERAPY CASE REPORTS STRATEGY - EXUDATIVE ARMD ICG- DIRECTED PDT TRIPLE THERAPY CASE REPORTS MULTIMODALITY IMAGING - CREATING STRATEGY - EXUDATIVE ARMD ICG-DIRECTED PDT TRIPLE THERAPY CASE REPORT 1.6 mm

8 STRATEGY - EXUDATIVE ARMD ICG-DIRECTED PDT TRIPLE THERAPY CASE REPORT STRATEGY - EXUDATIVE ARMD ICG-DIRECTED PDT TRIPLE THERAPY CASE REPORT THERAPY CASE REPORT THERAPY CASE REPORT MULTIMODALITY IMAGING - CREATING STRATEGY - EXUDATIVE ARMD ICG- DIRECTED PDT TRIPLE THERAPY CASE REPORT MULTIMODALITY IMAGING - CREATING STRATEGY - EXUDATIVE ARMD ICG-DIRECTED PDT TRIPLE THERAPY CASE REPORT THERAPY CASE REPORT THERAPY CASE REPORT THERAPY CASE REPORT Mark H. NelsonMD MBA Mark H. NelsonMD MBA

9 Multimodality imaging Enables a complete view of the: Vitreous Retina Choroid Heidelberg HRA+OCT Spectralis Has six different modalities to assess the eye. Fluorescein Angiography ICG Angiography Auto fluorescence Red Free Infrared Spectral Domain OCT FA-ICG-OCT in AMD using HRA+Spectralis OCT Looking for small changes with precision eye tracking Detailed images with noise reduction 3D volume scan A-scans/second FA-OCT provides the exact location of the cross section image ICG provides clear view of the choroid PROPERTIES of ICG vs. FA dye APPLICATIONS of DUAL MODALITY RAP and RCA Lesions ICG dye Molecular weight 775 KD Wavelength nm absorption nm emission Dye does not diffuse into choriocapillaries FA dye Molecular weight 375 KD Wavelength 494 nm absorption 521 nm emission Fast rate of leakage ICG DYE ( Indocyanine green ) is useful for Identifying: - RAP Lesions (Retinal angiomatous proliferation) - RCA Lesions (Retinal choroidal anastomosis) - CSR (Central serous retinopathy) - Occult CNV - Polypoidal Choroidal Vasculopathy RAP and RCA Lesions CSR OCCULT CNV

10 POLYPOIDAL VASCULOPATHY APPLICATIONS of DUAL MODALITY Fluorescein dye is used to identify Retinal Diseases: CLASSIC CNV Classic CNV CME Diabetic Retinopathy Optic Nerve Swelling Retinal Tumors Vein Occlusions Artery Occlusions And more CLASSIC CNV OPTIC NERVE SWELLING TECHNIQUE FOR MULTIMODALITY FA-ICG-OCT IR-OCT and AF-OCT photos of both eyes are taken A mixture of FA and ICG dye is prepared in a 1 to 2 ratio A vein is found the needle is taped in place. The focus is set on ICG ¾ of the dye is being injected into the vein A seconds movie of simultaneous FA-ICG of the primary eye is than taken. A Volume OCT-ICG photo is taken followed by Volume OCT-FA TECHNIQUE FOR MULTIMODALITY FA-ICG-OCT The rest of the dye is being injected at this point A comparison of the Volume OCT-ICG with previous exam is taken Volume OCT-ICG and comparison with previous exam is being taken of the secondary eye Volume OCT-FA follows Several single FA-OCT and ICG-OCT photos are also taken. STRATEGY - EXUDATIVE ARMD Photos by Anda Krist, CRA, COT mnelson@retinanet.net