Maculogix Honorarium Speaker Science Based Health Honorarium Speaker OptoVue Honorarium Speaker B&L Honorarium Advisor Allergan. Genentech.

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1 Disclosures Commercial Interest Nature of Relevant Financial Relationship Fundus evalua1on from Photography to Op1cal Coherence Angiography Leo Semes, OD, FAAO Heart of America 2018 Maculogix Honorarium Speaker Science Based Health Honorarium Speaker OptoVue Honorarium Speaker B&L Honorarium Advisor Allergan Genentech Regneneron Shire ZeaVision Reichert/Ametek HPO Honorarium Honorarium Honorarium Honorarium Honorarium Honorarium Stock options Advisor Advisor Speaker Speaker Advisor Speaker Advisor Introduc1on Documenta1on of the ocular fundus began with drawings Ocular fundus evalua1on and documenta1on Photography observa1on / documenta1on for progression Evolved to fundus photography (several itera1ons) Was supplemented by fluorescein angiography Became enhanced by OCT Is augmented by OCT-A Fluorescein Angiography to confirm diagnoses and direct treatment Mechanism, the dye mixes with serum to demonstrate the integrity (or loss thereof) of the re1nal and choroidal circula1on); a dynamic process. Ocular fundus evalua1on and documenta1on Op1cal coherence tomography (OCT) in vivo histology Op1cal coherence tomography angiography (OCT-A) Imaging of the vasculature landscape of the re1na and choroid Mechanism uses mo1on of the RBCs to trace the vasculature Ocular fundus evalua1on and documenta1on Op1cal coherence tomography (OCT) in vivo histology Op1cal coherence tomography angiography (OCT-A) Imaging of the vasculature landscape of the re1na and choroid Mechanism uses mo1on of the RBCs to trace the vasculature It s all about the capillaries 1

2 70s WF Drusen & GA in AMD Several year follow-up of long-standing dry AMD VA = 20/40 (stable over the last 4 years) OD fundus from 07/15 High-resolu1on OCT scan of the previous Key features Sec1on through the center of the macula (inferior to superior going from L to R on the scan) Vitreo-macular adherence without disrup1on of macular contour Regular arrangement of the inner re1nal layers Disrup1on of the outer re1nal layers Dis1nct drusen presence consistent with fundus appearance Area of geographic atrophy; absent RPE allows greater visibility deeper into the choroid. Color version of the previous Note the signal strength (8/10) Appreciate the improved resolu1on of the B/W version (the GA is more difficult to appreciate. 5-line scans can be oriented in any direc1on. At the bodom of the scan is where you can make your interpreta1on Stargardt disease (outer re1nal and RPE changes) 33 WM History of blurry vision and previous spectacle correc1on lost or broken Vague but apparently noncontributory family ophthalmic and personal medical histories BSCVA 20/200 in each eye with minimal refrac1ve correc1on 2

3 Good signal strength Evident vitreous condensa1ons Obvious broadened foveal contour Greatly disrupted outer re1nal layers Laser injury with RPE and outer re1nal remodeling Absent RPE with greater visibility of the choroid Compare to clinical findings 52 WM History of accidental laser exposure X 5 years with immediate VA reduc1on & no improvement subsequently. (5/200) Close up of right macula Note RPE (if its black its remodeling) 16 High-resolu1on scans showing dimension of the laser injury lesion. Note the disorganiza1on of the outer re1na corresponding to other clinical findings. 17 Another cross-sec1on through the right macula showing thickened inner re1na and demonstra1ng vitreomacular adherence. The outer re1na is disturbed, as well. 20 WM Laser injury to face with both eyes poten1ally involved (Micra laser with a legend amplifier, 800nm, generally set at 2.5 wads, mode lock pulse laser) Persistent alerimage; no further VA reduc1on subjec1vely VA 20/20 in each eye

4 Ini1al presenta1on (within hours of the incident) Good signal strength Minimal disrup1on of PIL OD 6-week F/U with ultra high resolu1on imaging Ver1cal orienta1on shows intact and fully formed PIL week F/U with ultra high resolu1on imaging Horizontal orienta1on shows residual but minimal disrup1on of PIL Vitreo-macular trac1on and adhesion 22 3-day history of reduced VA OD 55 WF VMT (high-resolu1on) 20/60 and 20/20 4

5 VMA (20/20) 55 BF FTMH (full-thickness macular hole; 20/200 GP 56 BF BF referred for imaging of Choroidal Nevus Choroidal nevus Healthy No medica1ons Histories non contributory VA 20/20 OD, OS; wears full-1me monovision CL correc1on IOP = 15/16 mm Hg (10 AM) Anterior segments unremarkable by slit-lamp microscopy 5

6 Wide-angle fundus photo OD OCT HD 5-line raster through nevus HD 5-line raster through nevus thickness measurement Case Example Op1c nerve head drusen (ONHD) (dis1nguishing from papilledema with the help of OCT) 16 YO WF RFV: update spectacle lens Rx Per1nent medical history: migraines Spectacle Rx X 3 years (low hyperopic refrac1ve correc1on) No medica1ons, allergies or contributory family history 6

7 Clinical findings Ultrasound -OD VA = 20/20, 20/25- Anterior segment findings unremarkable OD & OS Tonometry 16 mm Hg OD, OS Dilated fundus examina1on OCT Op1cal Coherence Tomography OD cube ONH / RNFL- OD Observa1ons? Anatomical correla1ons Dis1nguishing between FA and OCTA OCTA FA/ICGA Non-Invasive X Dye-Free X Displays paderns of leakage, pooling, staining X Displays re1nal and choroidal FA: Re1nal X vasculature ICGA: Choroidal Provides flow informa1on at a fixed point in 1me X Allows segmenta1on of re1nal layers X Imaging 1me 6 seconds per eye minutes Prone to mo1on ar1fact X 7

8 Ocular fundus evalua1on and documenta1on Op1cal coherence tomography (OCT) in vivo histology Op1cal coherence tomography angiography (OCT-A) Imaging of the vasculature landscape of the re1na and choroid Mechanism uses mo1on of the RBCs to trace the vasculature It s all about the capillaries OCTA Clinical Applica1ons Inner Re1na Disorders - Diabe1c Re1nopathy (DR) - Prolifera1ve Diabe1c Re1nopathy (PDR) - Macular Telangiectasia - Branch Re1nal Vein Occlusion (BRVO) - Macular Pucker - Coat s Disease - Re1nal Ischemia OCTA Clinical Applica1ons Outer Re1na Disorders - Choroidal neovasculariza1ons (CNV) Type I Type II Type III (RAP) Mixed Type I and II Foveal hypoplasia (?) Amblyopia Follow Treatment More Closely with Non-Invasive Imaging CNV Baseline 24 Hours Post Injection 7 Days Post Injection 30 Days Post Injection Previously diagnosed patient. Images courtesy of Bruno Lumbroso, MD Normal Re1nal Vasculature Re1na Choroid ANGIOVUE IMAGE INTERPRETATION Superficial Capillary Plexus 3µm Below ILM 15 µm Below IPL Deep Capillary Plexus 15µm Below ILM 70 µm Below IPL Outer Retina 70µm Below IPL 30 µm Below RPE Reference Choriocapillaris 30 µm Below RPE Reference 60 µm Below RPE Reference 8

9 New vessels develop in the choroid New vessels located BELOW RPE and ABOVE Bruch s membrane Type 1 Occult CNV Type 1 Occult CNV RPE Bruch s Membrane Choroid Fluorescein Angiography Superficial Capillary Plexus Choriocapillaris Type 2 Classic CNV New vessels develop in choroid New vessels located BELOW the RPE and ABOVE Bruch s membrane Type 2 Classic CNV RPE Bruch s Membrane Choroid Fluorescein Angiography Superficial Capillary Plexus Choriocapillaris Dual-Modality Imaging of Choroidal Neovasculariza1on Type 3 CNV (RAP) - mul1-modal imaging Superficial Deep Outer Retina Choriocapillaris OCT Angiography Angioflow images En Face OCT Previously diagnosed patient. Images courtesy of Nadia Waheed, MD E., F. OCTA showing intrare1nal NV 9

10 Type 3 CNV response to aflibercept treatment Diabe1c Re1nopathy Re1nal capillary non-perfusion seen as blackened area without blood flow outside FAZ Microaneurysms Enlarged FAZ Superficial Capillary Plexus Deep Capillary Plexus Choriocapillaris Previously diagnosed patient. Images courtesy of Nadia Waheed, MD Dual-Modality Imaging of Diabe1c Re1nopathy Non-Prolifera1ve Diabe1c Re1nopathy Superficial Deep Outer Retina Choriocapillaris OCT Angiography Angioflow images En Face OCT En Face OCT images Fluorescein Angiography Superficial Capillary Plexus Deep Capillary Plexus Diabe1c Re1nopathy Branch Re1nal Vein Occlusion Fluorescein Angiography 6x6 mm Macula Scan OCT Angiography Enlarged FAZ Telangiectatic Vessels Capillary Nonperfusion Superficial Capillary Plexus Previously diagnosed patient. Images courtesy of Pravin Dugel, MD Optic Disc Fluorescein Angiography Superficial & Deep Capillary Plexus 10

11 Branch Re1nal Vein Occlusion Glaucoma 4.5x4.5 mm Optic Disc Scan OCT Angiography: Vascular density Normal Optic Disc Moderate Glaucoma Severe Glaucoma OCT: Structure Fluorescein Angiography Superficial & Deep Capillary Plexus Trend Analysis: GCC + ONH Optic Disc En Face View Previously diagnosed patient. Images courtesy of Michel Puech, MD, FRCS Auto Segmenta1on of Re1nal Layers Layer indicators provide a reference to the re1nal layer displayed January 14, 2107 CLINICAL EXAMPLE Red: Choriocapillaris Yellow: Outer Re1na White: Superficial Capillary Plexus Purple: Deep Capillary Plexus 11

12 Outside the posterior pole RB 9/24/1938 (AA/F) Applica1on of OCT to Glaucoma How it helps to answer the ques1on (diagnosis / follow-up) Seen at UAB clinics X many years (XXX record #; now at XXXXXXX) HISTORY: (3/99) (-) Family Hx. HTn X 11 yrs.; [-] Diabetes Med: tenormin; walks and exercises; [-] tobacco, alcohol BSCVA 20/20 in each eye despite early lens changes ANTERIOR SEGMENT : Unremarkable IOP (OD) IOP (OS) RB 9/24/1938 (AA/F) 3/00 Diazyde added 4/01 Atennolol added 4/02 D/C tenromin, add :premarin 4/03 BP = 114/70 5/04 BP = 130/80 HX: Brother Dx w/glaucoma; pt becomes GS (Asymmetric cups) ONH (5/2006) PACHYMETRY: 642/591) RB 9/24/1938 (AA/F) 12

13 VF Series 1: 2004 (baseline) VF Series 2: 2005 RB 9/24/1938 (AA/F) - IOP Range Frequency Doubling Technology (FDT) Perimetry Results (4/6/05) (OD) (OS) Threshold No flags (OD, OS) PACHYMETRY: 642/591 (4/6/05) Retest! (OS) Dilemma? or Direction? RB 9/24/1938 (AA/F) VA 20/20 to 20/20- with mild NS changes BP good PR: 60 4/08 As OHT (IOP range 17-24, 15-21): Risk calcula1on (1-5% - low) 13

14 VF Series 3: 2/ (Bad day or progression? Fundus photos 4/5/2006 5/10/2011 Repeat the VF! (5/10/2011) Change analysis 5/10/2011 look closely OS OD 14

15 5/10/2011 look closely Treat or not? Need more evidence? OCT RNFL MRNFL (GCC) ONH 5/10/2011 look closely 15

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17 Glaucoma Rapid explosion of informa1on in he OCTA arena Br J Ophthalmol doi: /bjophthalmol Op1cal coherence tomography angiography of foveal hypoplasia Kaivon Pakzad-Vaezi1, Pearse Keane1, 2, João Nobre Cardoso1, Catherine Egan1, Adnan Tufail1 Corresponding author: Dr Kaivon Pakzad-Vaezi, Department of Medical Re1na, Moorfields Eye Hospital, 162 City Road, London EC1V 2PD, UK. Published Online First 29 November 2016 Conclusions The superficial re1nal capillary plexus is present in cases with foveal hypoplasia, while the deep re1nal capillary plexus is absent to varying degrees. Our findings support the hypothesis that an intact foveal avascular zone of the deep capillary plexus allows for outer re1nal photoreceptor specialisa1on to occur unimpeded, resul1ng in preserved visual acuity, while this process may be inhibited by an absent deep capillary foveal avascular zone with resultant poor vision. Rapid explosion of informa1on in he OCTA arena Br J Ophthalmol doi: /bjophthalmol DiagnosKc ability of peripapillary vessel density measurements of opkcal coherence tomography angiography in primary openangle and angle-closure glaucoma Harsha L Rao1, Sujatha V Kadambi1, Robert N Weinreb2, Narendra K PuSaiah1, Zia S Pradhan1, Dhanaraj A S Rao1, Rajesh S Kumar1, Carroll A B Webers3, Rohit SheSy1 Dr Harsha L Rao, Narayana Nethralaya, 121/C, Chord Road, 1st R Block, Rajajinagar, Bangalore , India. Published Online First 29 November 2016 Conclusions Diagnos1c ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnos1c abili1es of vessel density measurements were comparable to RNFL measurements in both POAG and PACG. Vessel density (OCTA) and VF loss correla1on in glaucoma Yarmohammadi A, et al., Rela1onship between Op1cal Coherence Tomography Angiography Vessel Density and Severity of Visual Field Loss in Glaucoma.Ophthalmology 2016;123:

18 Glaucoma applica1on #1. PCD example Peripapillary capillary density (PCD) What this is important ONH blood supply is derived mainly from choriocapillaris Emerging evidence for an early structural indicator in glaucomatous damage and an index for progression. Conclusions PCD displayed significant correla1ons with morphological and func1onal indices and exhibited diagnos1c capabili1es comparable to currently employed clinical variables. Our preliminary results suggest that PCD analysis may prove to be a useful tool in monitoring POAG across stage and iden1fying early POAG. Geyman LS, et al. Peripapillary perfused capillary density in primary open-angle glaucoma across disease stage: an op1cal coherence tomography angiography study. Br J Ophthalmol doi: /bjophthalmol Akil H, et al. Op1cal Coherence Tomography Angiography of the Op1c Disc; an Overview. J Ophthalmic Vis Res 2017; 12(1): Peripapillary capillary density (PCD) Conclusions. Diagnostic ability of peripapillary vessel density parameters of OCTA, especially the inferotemporal sector measurement, was good in POAG and PACG. Diagnostic abilities of vessel density measurements were comparable to RNFL measurements in both POAG and PACG. Glaucoma applica1on #2. Macular capillary density What this is important Ganglion-cell layer thickness is a measurable parameter and now demonstrated to correlate with capillary investment Emerging evidence correlates two structural indicators in early glaucomatous damage Roa HL, et al. Diagnos1c ability of peripapillary vessel density measurements of op1cal coherence tomography angiography in primary open-angle and angle-closure glaucoma. hdp://bjo.bmj.com/content/early/ 2016/11/29/bjophthalmol long Ichiyama Y, et al. Capillary Dropout at the Re1nal Nerve Fiber Layer Defect in Glaucoma: An Op1cal Coherence Tomography Angiography Study. J Glaucoma Sep 2. Glaucoma applica1on #3. RNFL capillary density What this is important RNFL (inner re1nal vasculature correla1on to RNFL loss) Microvascular compormise may follow RNFL damage (NTG study) Emerging evidence correlates with two structural indicators in early glaucomatous damage Ichiyama Y, et al. Capillary Dropout at the Re1nal Nerve Fiber Layer Defect in Glaucoma: An Op1cal Coherence Tomography Angiography Study. J Glaucoma Sep 2. Lee EJ, et al. Microvascular Compromise Develops Following Nerve Fiber Layer Damage in Normal- Tension Glaucoma Without Choroidal Vasculature Involvement. J Glaucoma Mar;26(3): doi: /IJG Glaucoma applica1on #4. Choroidal capillary density What this is important Choroidal (choriocapillaris) circula1on can be visualized by OCT-A and correlates with PCD Conclusions. FAZ and CCVD are interchangeable between the 3Å~ 3 mm and 6Å~ 6 mm macular scan sizes. The VD differences between the two different scan sizes are not clinically meaningful. The macular perfusion parameters presented good but not perfect reliability, which should be acknowledged in clinical prac1ce. Dong J, et al. Interchangeability and reliability of macular perfusion parameter measurements using op1cal coherence tomography angiography. hdp://bjo.bmj.com/content/early/ 2017/03/23/bjophthalmol

19 Recent reports on OCT-A OCT-A for assessing macular vessel density as an index for progression in Stargardt disease (ARVO May hdp:// online/%7b4efd2a90-d293-4ef8-bd11-3b44c76451a4%7d/octa-used-to-assessmacular-vessel-density-in-stargardt-disease utm_source=selligent&utm_medium= &utm_campaign=ophthalmology%20 news&m_bt= Recent reports on OCT-A and glaucoma OCT-A for assessing macular vessel density as an index for progression in Stargardt disease (ARVO May hdp:// online/%7b4efd2a90-d293-4ef8-bd11-3b44c76451a4%7d/octa-used-to-assessmacular-vessel-density-in-stargardt-disease? utm_source=selligent&utm_medium= &utm_campaign=ophthalmology%20 news&m_bt= THANK YOU! 19