Objective Assessment of Macula and Optic Nerve

Transcription

1 Objective Assessment of Macula and Optic Nerve Jerry Sherman Disclosure: Dr. Sherman has lectured and received honorarium from Carl Zeiss Meditec, Topcon, Optovue, Optos, and PHP, Diopsys, Eye Solutions,Quantel, MacuHealth and received support for Retina Revealed from all and also from Heidelberg and DGH BEYOND OPHTHALMOSCOPY

2 Helmholtz Invented the Ophthalmoscope in the 1860 s With an SD OCT, we are learning that most retinal disorders are invisible to ophthalmoscopy in the early stages but easily detected with SD OCT. 150 years after Helmholtz, SD OCT is rapidly relegating ophthalmoscopy to a much more modest role in diagnosis.

3 Commercially available SD-OCTs: Cirrus HD-OCT (Zeiss) 3D-OCT-2000 (Topcon) RTVue-100 (Optovue) Spectral OCT/SLO ivue (Optovue) Spectralis (Heidelberg) BEYOND OPHTHALMOSCOPY

4 Newest, least expensive SD OCT A Game Changer

5 Case great for mobile applications

6 EYE AND BRAIN (2013) February 13, 2013

7 Normal Subjects: 125 of 126 correctly identified as normal. Retinal and/or optic nerve disease: 97 of 101 patients correctly identified as having the disease. Retinal Pathology: 64 of 67 patients correctly identified as having a retinal disease. Optic Nerve Pathology: 45 of 50 patients correctly identified as having an optic nerve disease. RESULTS

8 Consideration of the junction between the inner and outer segments a.k.a. the Photoreceptor Integrity Line (PIL) may be useful Histological Section Normal OCT Image PIL Inner Segments Outer Segments RPE Retinal Pigment Epithelium Although the photoreceptor integrity line, or the PIL (defined as the junction between the inner and outer segments) is barely visible in most histological sections, it is highly prominent in normal SD OCTs. The PIL, as shown above, should be continuous throughout the entire scan in normal eyes. The PIL is considered by some as a mere artifact that is due to the difference in the index of refraction of the inner and outer segments but this artifact is remarkably useful in SD OCT interpretation.

9 Blood Vessel ILM Reflection Foveal Pit ILM Reflection Blood Vessel ILM Reflection RNFL PIL RNFL Fovea Shadow Shadow

10 Excerpt from Direct Ganglion Cell Assessment with the RTVue by Optovue: The Ganglion Cell Complex Analysis by Mike Sinai, Ph.D. Retinal ganglion cells encompass three layers in the retina: 1) the retinal nerve fiber layer (RNFL) is made up of the ganglion cell axons 2) the ganglion cell layer (GCL) is made up of the ganglion cell bodies, 3) The inner-plexiform layer (IPL) is made up of the ganglion cell dendrites. All three layers, collectively known as the ganglion cell complex (GCC), become thinner as the ganglion cells die. The RTVue and ivue directly measure the thickness of these three layers and provide a unique analysis of the percent loss of these layers compared to an extensive normative database. The results are presented as significant loss from normal (Significance) in order to aid in the clinical interpretation.

11 RETINAL & OPTIC NERVE DISEASE

12 Dawn of Pharmaco-Genetics Evolving Standard of Care in AMD New knowledge and new technology creates additional opportunity but also new responsibility.

13 Great Science - Key AMD genes COL8A1 TIMP3 LIPC APOE CETP ABCA1 CFH CFH CFI CFB C2 C3 Complement ARMS2 ARMS2 Oxygen Metabolism C3 C2 CFB CFI TIMP3 COL8A1 LIPC APOE CETP ABCA1 Extracellular Matrix Cholesterol Metabolism Macula Risk NXG 12 genes

14 Treatment Response to Antioxidants and Zinc Based on CFH and ARMS2 Genetic Risk Allele Number in the Age-Related Eye Disease Study Ophthalmology Sept 2014 Carl C. Awh, MD,1 Steven Hawken, MSc,2 Brent W. Zanke, MD, PhD2,3,4 Objective: To evaluate the impact of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk alleles on the observed response to components of the Age-Related Eye Disease Study (AREDS) formulation. Design: Genetic and statistical subgroup analysis of a randomized, prospective clinical trial. Participants: White patients from the AREDS with category 3 or 4 age-related macular degeneration (AMD) with available DNA (n= 989). Methods: Four genotype groups based on CFH and ARMS2 risk allele number were defined. Progression to advanced AMD was analyzed by genotype and treatment using Cox proportionate hazards estimates and 7-year events.

15 Main Outcome Measures: The effect of predefined genotype group on treatment-specific progression to advanced AMD. Results: Patients with 2 CFH risk alleles and no ARMS2 risk alleles progressed more with zinccontaining treatment compared with placebo, with a hazard ratio (HR) of 3.07 (P =0.0196) for zinc and 2.73 (P =0.0418) for AREDS formulation (AF). Seven-year treatment-specific progression rates were: placebo, 17.0%; zinc, 43.2% (P = 0.023); and AF, 40.2% (P = 0.039). Patients with 0 or 1 CFH risk alleles and 1 or 2 ARMS2 risk alleles benefited from zinccontaining treatment compared with placebo, with an HR of for zinc (P = 0.012) and for AF (P=0.0254). Seven-year treatment-specific AMD progression rates were as follows: placebo, 43.3%; zinc, 25.2% (P =0.020); and AF, 27.3% (P=0.011). Zinc and AF treatment each interacted statistically with these 2 genotype groups under a Cox model, with P values of and , respectively. For patients with 0 or 1 CFH risk alleles and no ARMS2 risk alleles, neither zinc-containing treatment altered progression compared with placebo, but treatment with antioxidants decreased progression (HR, 0.380; P = 0.034). Sevenyear progression with placebo was 22.6% and with antioxidants was 9.17% (P =0.033). For patients with 2 CFH risk alleles and 1 or 2 ARMS2 risk alleles, no treatment was better than placebo (48.4%). Conclusions: The benefit of the AREDS formulation seems the result of a favorable response by patients in only 1 genotype group, balanced by neutral or unfavorable responses in 3 genotype groups. Ophthalmology 2014; by the American Academy of Ophthalmology.

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17 Take Home Message

18 Heterogeneous response to zinc/antioxidants within AREDS Category 3 patients Genotype Group Better Worse Average ->

19 Contact Information for Arctic Group of Companies Macula Risk - Vita Risk Customer Service Or visit us at Kathy Rymer-Director of Sales

20 Progression to Vision Loss (%) GDT more than doubles the efficacy Placebo AREDS Genome Directed Therapy Years

21 2013

22 Topcon 1 line raster OCT OD 2013 High risk CFH alleles: Zinc results in faster progression!

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24 MacuHealth Ocular Treatment Scientifically Proven Focused Formula 10 mg Meso-Zeaxanthin (MZ) 10 mg Lutein 2 mg Zeaxanthin MZ has proven to be the key Carotenoid in the fight on AMD No Contraindications MZ is the dominant macular protective pigment found in the center of the macula When Sherman pops a pill, it contains all 3 critical carotenoids. Triplets- isomers of each other.

25 Contact information: Eye Solutions Technologies, LLC North 17th Drive, Suite 6 Phoenix, AZ 85027

26 True or False: If the retina looks normal with an ophthalmoscope, the retina is normal. FALSE! BEYOND OPHTHALMOSCOPY

27 Consideration of the junction between the inner and outer segments a.k.a. the Photoreceptor Integrity Line (PIL) may be useful Histological Section Normal OCT Image PIL Inner Segments Outer Segments RPE Retinal Pigment Epithelium Although the photoreceptor integrity line, or the PIL (defined as the junction between the inner and outer segments) is barely visible in most histological sections, it is highly prominent in normal SD OCTs. The PIL, as shown above, should be continuous throughout the entire scan in normal BEYOND eyes. The PIL is considered by some as a mere artifact that is due to the difference OPHTHALMOSCOPY in the index of refraction of the inner and outer segments but this artifact is remarkably useful in SD OCT interpretation.

28 Does the OCT match the fundus? Yes! Fundus Autofluorescence So what is it? Achromatopsia The FAF images reveal a hypoautofluorescent oval zone in both eyes which corresponds to the sharply delineated rectangular hyporeflective space in the OCT. This patient s sister is also diagnosed with achromatopsia. Normal Control RPE Complex with underlying Bruch s Membrane PIL Outer Limiting Membrane BEYOND OPHTHALMOSCOPY

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32 Spectralis Cirrus BEYOND OPHTHALMOSCOPY

33 This is Fundus Autofluorescence BEYOND Retina Revealed OPHTHALMOSCOPY Sherman and Sadda

34 What is Fundus Auto Fluorescence? Retina Revealed BEYOND Sherman OPHTHALMOSCOPY and Sadda

35 OD fundus color

36 AF OD

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42 l 5 y/o daughter 8 y/o Son Normal External limiting membrane Posterior Hyaloid Ganglion cell layer External Limiting Membrane Inner Plexiform Layer RNFL Vitreous Inner Nuclear Layer Outer Nuclear Layer Outer Plexiform Layer choroid PIL

43 Patient #1 OD Patient #2 OD Patient #3 OD

44 5 y/o daughter OD vs Normal Does photoreceptor degeneration result in debris accumulating on ELM? 5 y/o daughter Normal External limiting membrane Posterior Hyaloid Ganglion cell layer External Limiting Membrane Inner Plexiform Layer RNFL Vitreous Inner Nuclear Layer Outer Nuclear Layer Outer Plexiform Layer choroid PIL A Novel Finding which may be a biomarker for very early degen in SD

45 4 y/o daughter OS Father OS ELM ELM PIL PIL

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47 Annidis MSI Capturing Data Fundus Camera Range OCT/SLO Green Yellow Amber Red1 Red2 Red3 Red4 Infrared1 Infrared2 Infrared3 The Annidis blue RHA line highlights is based on the Multispectral near Gaussian imaging. distribution What of does the this human mean? eye s sensitivity to light. Traditional The instrument Fundus uses Cameras up to12 wavelengths mimic this and of color reveal generated images similar by LEDs. to what LEDs is generate OCT/SLO technology utilize a single very narrow wavelength in the infrared seen by zone the fairly human narrow that eye. bandwidths. allow Blue, cross Red, This sectional and creates Green a information light series sensors of monochromatic of have the retina been used en face to be in obtained. fundus fundus cameras. spectral Beyond slices which 650nm, are traditional processed fundus and aligned imaging and cameras results lose in enhanced sensitivity. differential visibility of key morphological structures throughout the depth of the retina and en face visualization of the RPE.

48 Case 1 Although traditional fundus photography (top left) and Optos Color Image (top right) yield some information about the deep lesions, the Annidis MSI yields important information about the deep lesions not clearly visible before. Color Composite Green Red4 Infrared3

49 The patient has hundreds of flat, coffee colored lesions of various sizes on her body which represent melanin deposition. These are generally termed café-au-lait spots. A much smaller number of lesions are somewhat raised and these represent cutaneous and subcutaneous neurofibromas. Both are common in NF type 1.

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51 Case 5 : Topcon 3D OCT Fundus Image OD BEYOND OPHTHALMOSCOPY

52 Case 5: Topcon 3D OCT Fundus Image OS BEYOND OPHTHALMOSCOPY

53 Optomap ResMax Auto-Fluorescence Images Bull s Eye Maculopathy OU Flash ERG Normal No history of Plaquenil use Accutane Toxicity? OD OS BEYOND OPHTHALMOSCOPY

54 Normal PIL Present ELM Present Patient PIL Present ELM Present PIL Missing A horizontal section through the fovea of the left eye reveals similar findings as displayed previously in the right eye. A small, but intact, PIL is present under the fovea and a perifoveal absence of the PIL is documented. With loss of the PIL, the intact external limiting membrane (ELM) appears to drape over the missing tissue. BEYOND OPHTHALMOSCOPY

55 VISUAL EVOKED POTENTIAL ASSESSMENT OF NEURO-VISUAL FUNCTION Electrical Imaging BEYOND OPHTHALMOSCOPY

56 VISUAL EVOKED POTENTIAL ASSESSMENT OF NEURO-VISUAL FUNCTION Jerome Sherman, OD SUNY Distinguished Teaching Professor BEYOND OPHTHALMOSCOPY COPE

57 BEYOND OPHTHALMOSCOPY

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59 Histological Section as Compared to the OCT Image Histological Section Normal OCT Image PIL Inner Segments Outer Segments RPE Retinal Pigment Epithelium Although the photoreceptor integrity line, or the PIL (defined as the junction between the inner and outer segments) is barely visible in most histological sections, it is highly prominent in normal SD OCTs. The PIL, as shown above, should be continuous throughout the entire scan in normal eyes. The PIL is considered by some as a mere artifact that is due to the difference in the index of refraction of the inner and outer segments but this artifact is remarkably useful in SD OCT interpretation. * The PIL as Revealed by SD OCT is available at: Add PIL Book Logo Link

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61 Older brother

62 Cirrus TM HD-OCT Horizontal Scan Image of Normal Control OD External Limiting Membrane PIL OS/RPE RPE/BM RPE Complex Although the retinal pigment epithelium (RPE) is only a single layer of cells, it appears as two reflective layers with a dark zone in between on high definition OCT scans. The inner reflection has been referred to by some authors as the outer segment-rpe interdigitation (OS/RPE) or Verhoeff s membrane. The outer reflection is the RPE/Bruch s membrane complex (RPE/BM). Note the two reflections from the RPE complex are only visible on high definition scans. On lower resolution OCT scans the RPE generally appears as one solid thick band.

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64 Younger brother Older brother

65 Case: Laurence-Moon Bardet-Biedl Polydactyly both patients had 24 digits at birth. Scars are visible on the hands where digits have been removed. Additional digits on the feet are still intact. Diagnosis Probable Laurence-Moon or Bardet-Biedl or LMBB syndrome and not autism! Genetic testing for the BBS1 gene is now available (Carver Nonprofit Genetic Tesitnig Lab at

66 ASSESSMENT OF NEURO-VISUAL FUNCTION perg Eye stimulation by a checkerboard pattern elicits a ganglion cell response known as PERG. Stimulus (Monitor) PERG is an accurate and objective indicator of ganglion cell and macular function. (ISCEV) Recording (Sensors) PERG can detect retinal dysfunction (OHT) before structural tests. (Parisi et al.)

67 ASSESSMENT OF NEURO-VISUAL FUNCTION Diopsys perg Electrodes Comfort Convenience Quality

68 Jerome Sherman, OD Now 2500 labeled retinal images BEYOND OPHTHALMOSCOPY

69 Case 1: Optovue Retina Map and Optomap AF OU In the OD above, the AF image appears normal but the OCT is clearly disrupted. In the OS below, both the AF image and the OCT reveal marked abnormalities of the RPE.