FALSE! True or False: Back to Basics. Key to Retinal Assessment: Making Visible what is Invisible Jerome Sherman

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1 Key to Retinal Assessment: Making Visible what is Invisible Jerome Sherman Disclosure: Dr. Sherman has lectured and received honorarium from Carl Zeiss Meditec, Topcon, Optovue, Optos, Eye Solutions, PHP, MacuHealth, ArcticDx, Diopsys, Annidis, Innova, and received support for Retina Revealed from all and also from Heidelberg and DGH. The Diagnosis of Retinal Disease Invisible to Ophthalmoscopy Jerome Sherman Structure Ophthalmoscopy Fundus photography Panoramic Imaging (Optos) Fluorescein Angiography B- scan ultrasound SD OCT & OCT A HRT and GDx FAF -Fundus autofluorescence Function Visual Acuity Pupils Fields, PHP, MAIA Color vision Contrast Sensitivity Rabin cone contrast ERGs EOG perg mf ERGs VEPS (pattern & flash) True or False: If the retina looks normal with an ophthalmoscope, the retina is normal. FALSE! Back to Basics But Why Back to Retinal Anatomy? Do you remember the 10 layers of the retina? Do you recall that the 9 neuro-sensory layers of the retina are invisible to ophthalmoscopy and only the RPE is visible? Have you ever said, Mrs. Jones, I am going to examine your rods and cones? 1

Page 8 Cirrus TM HD-OCT Horizontal Scan Image of Normal Control OD

com External Limiting Membrane OS/RPE RPE/BM RPE Complex Although the

appears as two reflective layers with a dark zone in between on high

The inner reflection has been referred to by some authors as the outer

The outer reflection is the RPE/Bruch s membrane complex (RPE/BM).

band. -A biomarker for rod and cone integrity Jerome Sherman, OD www.

Middle Retina Exudates (in diabetes) Retinoschisis Outer Retina

macula holes Page 10 Case 1: Horizontal Scan Images OD Since A horizontal

2 Page 8 Cirrus TM HD-OCT Horizontal Scan Image of Normal Control OD Photoreceptor Integrity Line as Revealed by SD OCT- lulu.com External Limiting Membrane 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) 1 or Verhoeff s membrane 2. The outer reflection is the RPE/Bruch s membrane complex (RPE/BM). 1 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. -A biomarker for rod and cone integrity Jerome Sherman, OD Spectralis Cirrus Invisible to Ophthalmoscopy Inner Retina/vitreous NFL VMT Middle Retina Exudates (in diabetes) Retinoschisis Outer Retina Photoreceptors () Early drusen Early choroidal neovascularization Early macula holes Page 10 Case 1: Horizontal Scan Images OD Since A horizontal the Osterberg OCT section graph through on the previous the hypoautofluorescent page does not show zone an in the abrupt FAF end image to cones (see page beyond 5) reveals the macula, a sharply the delineated sharply delineated rectangular end hyporeflective of the as demonstrated space under the here fovea is in not the anticipated. right eye. Hyporeflective Space 2

Image of Right Eye Absent Patient Normal

RPE RPE End of When compared to a normal

cones is important in the interpretation

3 Page 9 The Osterberg Graph Patient vs. Normal Control Topcon 3D OCT Radial Scan Image of Right Eye Absent Patient Normal Control RPE External Limiting Membrane RPE RPE End of When compared to a normal control, the abnormalities in the patient s OCT scan are more obvious. Unlike the normal control where the is present throughout, the patient s was absent throughout the scan except a small segment under the fovea. RPE Only 5% of photoreceptors in the retina are cones, and these are concentrated at the fovea. As reported by Osterberg in 1935, the density of cones drops off rapidly (but not abruptly) just several degrees from the fovea, and rods begin to predominate outside of the central 5 degrees or so. This known distribution of rods and cones is important in the interpretation of the in SD OCTs. The width of the OCT section (6mm) is denoted on the Osterberg graph by the vertical dashed green lines. Osterberg GA. Topography of the Layers of rods and cones in the human retina. Acta Ophthalog 1935 RPE RPE RPE ELM Normal Control Residual cones Images from the right eye above and left eye below with a higher resolution Raster image. There is evidence of some cones being present, which explains why the vision is relatively good. Residual cones Patient #2 LMBB: OCT OS Older brother 3

4 Younger brother Older brother Younger brother Older brother What s missing? 22 Additional Clue Polydactyly patient had 24 digits at birth and had 4 removed! What s missing? 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

8 y/o Son fundus OD 8 y/o Son: [AF] OD KEY: Standard

Photography A comparison of standard fundus photos to

round and many are fish tail or pisciform in shape,

quite typical of inherited retinal degenerations.

Topcon Fundus Photos OD and OS 5 y/o daughter 8 y/o Son

Ganglion cell layer External Limiting Membrane Inner

Nuclear Layer Outer Plexiform Layer choroid Case 2(5 yo

5 8 y/o Son fundus OD 8 y/o Son: [AF] OD KEY: Standard Photo Auto Fluorescence Case 1(8 yo son): Fundus Photography A comparison of standard fundus photos to AF images clearly reveals unmistakable abnormalities in the AF images only. Note that the small hyper-af lesions are often not round and many are fish tail or pisciform in shape, suggesting perhaps the fish tail lesions in Stargardt s Disease with fundus flavimaculatus. (link to RR #14) The symmetry of the AF findings are quite typical of inherited retinal degenerations. (see RR 54 part 1 and part 2) l Case 2(5 yo daughter): Topcon Fundus Photos OD and OS 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 Case 2(5 yo daughter): Above are the fundus photos of the five year old daughter. She had no symptoms but best corrected VA was about 20/40 in each eye. The images above reveal normal white glistening reflections off the internal limiting membrane in each eye. This is an expected finding in young children. The fundus images were interpreted as essentially normal in both eyes. 5

Case 2(5 yo daughter): Optomap FAF Image OD and OS Case 2(5 yo daughter):

The AF images reveal a subtle macula bulls eye in each eye.

Case 3(4 yo daughter): Fundus Photography Case 3(4 yo daughter): Topcon 3D OCT

the color fundus photos or in the AF images in the 4 yo daughter.

Cooperation improved for the OCT images.

irregular and hyper-reflective here in the right eye.

cell layer External Limiting Membrane Inner Plexiform Layer RNFL Vitreous

6 Case 2(5 yo daughter): Optomap FAF Image OD and OS Case 2(5 yo daughter): Topcon 3D OCT OS RPE ELM The ELM is abnormal in both grey scale and in color. The AF images reveal a subtle macula bulls eye in each eye. Note the hyper-af ring around the macula in each eye. This pattern is abnormal. Case 3(4 yo daughter): Fundus Photography Case 3(4 yo daughter): Topcon 3D OCT OD KEY: Standard Photo Auto Fluorescence No marked abnormality is obvious in the color fundus photos or in the AF images in the 4 yo daughter. RPE ELM With parental consent, chocolate was used to bribe the 4 yo. Cooperation improved for the OCT images. As revealed in her 5 yo sister, the is somewhat thin and the ELM is thickened, irregular and hyper-reflective here in the right eye. 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 Introducing the Rabin Cone Test choroid Inner Nuclear Layer Outer Nuclear Layer Outer Plexiform Layer Early Disease Detection & Ophthalmic Health Management Jerry Sherman, OD A Novel Finding which may be a biomarker for very early degen in SD 6

Enough to Measure Subtle Changes in Cone Function Based on Clinical

Validated Patterns of abnormalities are emerging: Early Stargard: very

Helmholtz Invented the Ophthalmoscope in the 1860 s With an SD OCT, we are

the early stages but easily detected with SD OCT.

(High-Speed) OCT System OCT-Angiography (OCTA) is a new imaging modality

circulation using the intrinsic motion of the blood cells in the vessel

Usually viewed in en face projections Unlike angiography, it requires no

Angiography features is not available for sales in US Not available for

Imaging of Choroidal Neovascularization using the Angiovue Imaging System

7 What is the Rabin Cone Test? Color Vision Test Sensitive Tests 3 colors at different contrast levels Enough to Measure Subtle Changes in Cone Function Based on Clinical Research Fast & Easy to Administer Medicare Reimbursable Independently Validated Patterns of abnormalities are emerging: Early Stargard: very reduced to red vs early traumatic brain injury: very reduced to blue 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. A New Way of Visualizing Vessels Optovue Avanti Spectral-Domain (High-Speed) OCT System OCT-Angiography (OCTA) is a new imaging modality until now only available in research prototypes Identify retinal circulation using the intrinsic motion of the blood cells in the vessel Unlike OCT, it acquires functional rather than structural information. Usually viewed in en face projections Unlike angiography, it requires no contrast medium and the data is three-dimensional and depth-resolved * OCT Angiography features is not available for sales in US Not available for sale in US En Face Visualization Superficial capillary Dual-Modality Imaging of Choroidal Neovascularization using the Angiovue Imaging System (3x3 mm) Superficial Deep Outer Retina Choriocapillaris Deep capillary Angioflow images En Face Visualization of layers based on retinal anatomy Outer Retina Choriocapillary En Face OCT images Not available for sale in US Not available for sale in US 7

Angioflow images of Normal Macula Angioflow images of

304 x 304 pixels (superficial capillary plexus) 6 x 6 mm,

available for sale in US 3 x 3 mm, 304 x 304 pixels (radial

5 mm, 304 x 304 pixels (radial peripapillary capillary)

52 YrO Male, 20/20 Tracking and Y-axis zoomed 13mm EHD Line.

8 Angioflow images of Normal Macula Angioflow images of Normal Optic Disc Not available for sale in US 3 x 3 mm, 304 x 304 pixels (superficial capillary plexus) 6 x 6 mm, 304 x 304 pixels (superficial capillary plexus) Not available for sale in US 3 x 3 mm, 304 x 304 pixels (radial peripapillary capillary) 4.5 x 4.5 mm, 304 x 304 pixels (radial peripapillary capillary) Enhanced HD Line Enhanced HD Line 12mm EHD Line. 52 YrO Male, 20/20 Tracking and Y-axis zoomed 13mm EHD Line. 45 YrO Female, Pacific Islands, -6.5D, Scanned through contact lenses. No Y-axis zoom Peripapillary Retinoschisis: A Novel Clinical Entity Revealed by OCT Case 1 Dx of Optic Neuropathies Beyond the Basics Case 50 GCC, VEP and RAPDx 8

Case 1: Zeiss VISUCAM Color Fundus Image OU Case 1: Zeiss Humphrey 30 2 Visual Fields OU Comparison

The GCC asymmetry is not reflected in the central threshold visual fields. Learn more about GCC link.

infectious T trauma A autoimmune M metabolic I inherited N neurodegenerative E endocrine S - senile

environmental S stress The iwellness exam was performed.

(ref ARVO abstract)although the SD OCT scans through the fovea were normal in each eye, the Ganglion

Quantitatively, a difference of greater than 10 um is clinically significant: here the right GCC is

Figure : VITAMINESx2 Once glaucoma has been ruled out, this mnemonic is helpful to remember other

in amplitude but delayed in the right eye.

9 Case 1: Zeiss VISUCAM Color Fundus Image OU Case 1: Zeiss Humphrey 30 2 Visual Fields OU Comparison of the right and left maculas and discs of each eye failed to reveal an explanation for her symptoms. The GCC asymmetry is not reflected in the central threshold visual fields. Learn more about GCC link. Case 1: Optovue iwellness OU Exam Page 23 When a RNFL loss is not due to Glaucoma V vascular I infectious T trauma A autoimmune M metabolic I inherited N neurodegenerative E endocrine S - senile V vitamin deficiency I inflammatory T toxic A allergic M mass lesions I idiopathic N nutritional E environmental S stress The iwellness exam was performed. This test has recently been reported to have 91% sensitivity and 99% specificity. (ref ARVO abstract)although the SD OCT scans through the fovea were normal in each eye, the Ganglion Cell Complex (GCC) was observably thinner in the right eye than in the left eye. Quantitatively, a difference of greater than 10 um is clinically significant: here the right GCC is 12 um thinner than the left. Figure : VITAMINESx2 Once glaucoma has been ruled out, this mnemonic is helpful to remember other possible etiologies of RNFL loss in non-glaucomatous optic nerve disorders. See details in : Logo Link to Book The Retinal Nerve Fiber Layer in Clinical Practice Case 1: Diopsys TM Nova DN OU In our 29 yo patient with blurred vision in her right eye, the VEPs are normal in amplitude but delayed in the right eye. Under high contrast conditions, the VEP P100 latency is delayed by 33 msec in the right eye when compared to the normal latency in the left eye. (Under standard Nova DN conditions, the entire pattern reversal stimulus contains 32x32 checks.) MAKE THE CHECKERBOARD LOOP CONTINUOUSLY Copyright Diopsys, Inc All Rights Reserved. Patent Pending. 9

VISUAL EVOKED POTENTIAL ASSESSMENT OF NEURO-VISUAL FUNCTION With the

00 D to compensate for the 1 meter working distance), the central 5

the fundus which corresponds to the macula.

transmitted through the visual pathway to the occipital lobe.

yellow) project onto about 50% of the occipital lobe!

the level of the occipital lobe with surface electrodes.

neuropathies affecting the papillo macular bundle (PMB) but also in

Diopsys VEPs are far simpler to obtain than traditional VEPs.

10 VISUAL EVOKED POTENTIAL ASSESSMENT OF NEURO-VISUAL FUNCTION With the patient s distance prescription in place ( with an additional D to compensate for the 1 meter working distance), the central 5 degrees of the visual field is focused onto the central 5 degrees of the fundus which corresponds to the macula. Action potentials are then generated by the ganglion cells which are transmitted through the visual pathway to the occipital lobe. Note that the central 5 degrees of the visual field ( in orange and yellow) project onto about 50% of the occipital lobe! Hence, the VEP is a test of macula and macula projections measured at the level of the occipital lobe with surface electrodes. VEPs are often far more sensitive than visual fields to optic neuropathies affecting the papillo macular bundle (PMB) but also in cases without any evidence of PMB compromise. Diopsys VEPs are far simpler to obtain than traditional VEPs. Case 1: Diopsys TM Nova DN OU OD vs. OS Composite 49.7 ms Delay Note the obvious difference in latency between the RE and LE when the VEPs are directly compared. OD vs. OS AF ResMax OU Best Best 10

OU Next Case AZOOR Acute Zonal Occult Outer Retinopathy Acute Zonal Occult Outer

stimulus for a mferg is shown in the left image above.

visual field (which is 54 degrees horizontal and 48 degree vertical).

The traditional color coding is employed: Bright colors correspond to high amplitude

White and red are hence large responses, light green is normal but blue is reduced.

11 OU Next Case AZOOR Acute Zonal Occult Outer Retinopathy Acute Zonal Occult Outer Retinopathy Patient now being treated with Immuran OD OD OS OS mferg The typical stimulus for a mferg is shown in the left image above. Usually, 103 hexagons pattern reverse from white to black and black to white in a pseudo-random sequence. The resultant response from the retina is a topographically accurate ERG from 103 different locations. The total field size often chosen is one that grossly corresponds to a standard 24-2 visual field (which is 54 degrees horizontal and 48 degree vertical). The amplitude of the mferg components are color coded for rapid interpretation. The traditional color coding is employed: Bright colors correspond to high amplitude areas whereas dark colors represent low amplitude zones. White and red are hence large responses, light green is normal but blue is reduced. The mfergs in November 2008 still appear normal in the right eye even though the patient was now symptomatic OD with reduced VA and a disorganized /junction OD. The mfergs above are quite similar to the mfergs under the same condition obtained 8 months earlier. In this case, the /junction appears to be more sensitive to dysfunction than the mferg. 11

12 Multi-Spectral Imaging MSI by Annidis Retinotoxic drug damage visualization 12

Case 1: Topcon 3D OCT Fundus Image OD Case 1: Topcon 3D OCT Fundus Image OS A 25 year old female presented with blurred vision in her

She was concerned about her The fundus through a dilated pupil was considered to be unremarkable with direct eyes because she was told

and with a BIO). type 1, sometimes develop visual problems. Previous eye exams failed to reveal any unusual findings.

00 unremarkable lens corrected in both her vision the right in her and right left eye eye. to 20/20 and a -0.

The slit lamp exam revealed several iris spots which were perhaps small Lisch nodules or just commonplace iris freckles.

appeared to be within normal limits. All retinal layers, including the Photoreceptor Integrity Line () appeared normal.

In addition to the retina, the vitreous and the choroid also appeared normal in each eye.

uses 10 different LEDs, each of a different color and somewhat different penetration range.

The Red and Infrared LEDs penetrate deeper into the retina and choroid and reveal abnormalities not visualized with the Green, Yellow

Annidis MSI Capturing Data Fundus Camera Range OCT/SLO Multi Spectral Imaging (MSI) Fundus Spectral Slices Green Yellow Amber

imaging. distribution What of does the this human mean? eye s sensitivity to light.

13 Case 1: Topcon 3D OCT Fundus Image OD Case 1: Topcon 3D OCT Fundus Image OS A 25 year old female presented with blurred vision in her right eye. She was concerned about her The fundus through a dilated pupil was considered to be unremarkable with direct eyes because she was told by her neurologist that patients with her disorder, neurofibromatosis ophthalmoscopy and with indirect ophthalmoscopy (with a 78D lens and with a BIO). type 1, sometimes develop visual problems. Previous eye exams failed to reveal any unusual findings. Fundus photography Our patient was was first also relieved judged when to a be unremarkable lens corrected in both her vision the right in her and right left eye eye. to 20/20 and a in her left eye also resulted in 20/20. The slit lamp exam revealed several iris spots which were perhaps small Lisch nodules or just commonplace iris freckles. Case 1: Topcon 3D OCT Image OU Case 1: Annidis MSI OD Color Composite Green Yellow Amber SD OCTs with the Topcon 3D OCT 2000 also appeared to be within normal limits. All retinal layers, including the Photoreceptor Integrity Line () appeared normal. The normal under the fovea predicts normal (corrected) visual acuity. In addition to the retina, the vitreous and the choroid also appeared normal in each eye. Red1 Red2 Red3 Red4 Infrared1 Infrared2 Infrared3 The Annidis Multi-Spectral Imaging, of our patient with NF. uses 10 different LEDs, each of a different color and somewhat different penetration range. The Green, Yellow and Amber LEDs reveal detailed information about the shallow retinal structures. The Red and Infrared LEDs penetrate deeper into the retina and choroid and reveal abnormalities not visualized with the Green, Yellow and Amber LEDs. Annidis MSI Capturing Data Fundus Camera Range OCT/SLO Multi Spectral Imaging (MSI) Fundus Spectral Slices Green Yellow Amber Infrared1 Infrared2 Infrared3 Red1 Red2 Red3 Red4 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. This simplistic diagram demonstrates the different penetration depths of several LEDs and the various images that may result. 13

Case 1: Annidis MSI OS Case 1: Annidis MSI OU Color Composite Green Yellow Amber Color Composite Green Red4 Infrared3 Red1

the Annids MSI to standard fundus photography.

Ten LEDs are used and then resulting images are displayed.

Color Composite Green Red3 Infrared3 Case 1 Case 1 Although traditional fundus photography (top left) and Optos Color Image

lesions not clearly visible before. Note similar findings in the left eye as well.

patient has hundreds of flat, coffee colored lesions of various sizes on her body which represent melanin deposition.

A much smaller number of lesions are somewhat raised and these represent cutaneous and subcutaneous neurofibromas.

RNFL loss can be detected and measured with OCT (and GDx) prior to ophthalmoscopic evidence leading to the early treatment of

14 Case 1: Annidis MSI OS Case 1: Annidis MSI OU Color Composite Green Yellow Amber Color Composite Green Red4 Infrared3 Red1 Red2 Red3 Red4 The Color Composite Image is a composite of the Green and Red1 Images, useful for comparing data acquired with the Annids MSI to standard fundus photography. Infrared1 Infrared2 Infrared3 Actual data from the left eye of our patient with NF. Ten LEDs are used and then resulting images are displayed. The Color Composite is a pseudo color image and is based upon the some of the data generated by the 10 LEDs. Color Composite Green Red3 Infrared3 Case 1 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. Note similar findings in the left eye as well. Color Composite Green Red4 Infrared3 Color Composite Green Red3 Infrared3 Some Examples Invisible to Ophthalmoscopy 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. RNFL loss can be detected and measured with OCT (and GDx) prior to ophthalmoscopic evidence leading to the early treatment of glaucoma and other optic neuropathies. Vitreal retinal traction can be documented with OCT prior to ophthalmoscopic evidence. Macula hole documented with OCT but invisible with O scope. Retinal splits at the outer and inner plexiform layer, which may not be detected with ophthalmoscopy, can easily be imaged with the use of OCT. Loss of photoreceptors are now easily detected with SD OCT and the loss may never be detected, even decades later, with ophthalmoscopy. Exudates in diabetes and other vascular disease can be detected with SD OCT far earlier than with O scope. 14

Spectralis OCT OS Page 15 Future VMT tx: Microplasmin injection Left Eye Is a

thrombolytic agent causing an enz pharmacological induced vitreolysis Nonsurgical

vitreous occurs LYSIS between vitreous cortex and ILM is the final outcome The

the presence of a normal foveal pit (see page 21).

pts had resolution of VMT In looking at pts w/o ERM, 37% had resolution of VMT 40%

without complications associated with PPV Packo & Jumper ASRS 2010 Left Eye Case 10:

Excavations Page 31 A 49-year-old male with history of a unilateral congenital optic

eye. Patient reports vision in both eyes is excellent.

Case 10: Topcon 3D OCT Demonstrating Elevation of the Retina Below the Disc Page 32

the macula, as well as a 6mm x 6mm scan box.

becomes mildly attenuated under the fovea and eventually disappears towards the

15 Spectralis OCT OS Page 15 Future VMT tx: Microplasmin injection Left Eye Is a recombinant truncated form of human plasmin that is active functions as a thrombolytic agent causing an enz pharmacological induced vitreolysis Nonsurgical PVD The enzymatic agents alter the biochemistry of vitreous Liquefaction of the vitreous occurs LYSIS between vitreous cortex and ILM is the final outcome The vertical section through the fovea depicts vitreal macular traction, which distorts the presence of a normal foveal pit (see page 21). Packo & Jumper ASRS 2010 Ocriplasmin (ThromboGenics) Could it be a future tx for symptomatic VMT? MIVI-TRUST N=~650 pts Microplasmin intravitreal injection vs placebo 26% of ALL tx pts had resolution of VMT In looking at pts w/o ERM, 37% had resolution of VMT 40% of pts with MH had a complete closure Improving VA and restoring ocular structures without complications associated with PPV Packo & Jumper ASRS 2010 Left Eye Case 10: Elevations vs. Excavations Page 31 A 49-year-old male with history of a unilateral congenital optic nerve abnormality detected five days after birth and enlarged blind spot in the left eye. Patient reports vision in both eyes is excellent. BCVA measured 20/15+2 OD and 20/15-1 OS. Case 10: Topcon 3D OCT Demonstrating Elevation of the Retina Below the Disc Page 32 Left Eye Excavation is attenuated Normal Fundus photo of the anomalous disc and of the macula, as well as a 6mm x 6mm scan box. The horizontal section through the macula reveals that the is normal temporally, becomes mildly attenuated under the fovea and eventually disappears towards the optic nerve head. Note the optic disc excavation nasal in this scan. For the full case study go to: Retina Revealed Case #8 - "Morning Glory" Disc Coloboma The sequential 2D horizontal sections (slices #74,75,76 and 77) demonstrate the presence of numerous subtle retinoschisis (see red arrows) changes at different levels of the retina inferior to the disc. Note the splitting and elevation of the retinal layers. 15

DGH B-Scan Scanmate Page 8 The DGH B-scan Scanmate below is a vertical slice

loss can be detected and measured with OCT (and GDx) prior to ophthalmoscopic

evidence. Macula hole documented with OCT but invisible with O scope.

detected with ophthalmoscopy, can easily be imaged with the use of OCT.

16 DGH B-Scan Scanmate Page 8 The DGH B-scan Scanmate below is a vertical slice through the optic nerve head and the retinoschisis inferior to the optic nerve head. Disc excavation Retinoschisis Some Examples Invisible to Ophthalmoscopy RNFL loss can be detected and measured with OCT (and GDx) prior to ophthalmoscopic evidence leading to the early treatment of glaucoma and other optic neuropathies. Vitreal retinal traction can be documented with OCT prior to ophthalmoscopic evidence. Macula hole documented with OCT but invisible with O scope. Retinal splits at the outer and inner plexiform layer, which may not be detected with ophthalmoscopy, can easily be imaged with the use of OCT. Loss of photoreceptors are now easily detected with SD OCT and the loss may never be detected, even decades later, with ophthalmoscopy. Exudates in diabetes and other vascular disease can be detected with SD OCT far earlier than with O scope. 16

Optomap Color Fundus Image of Right Eye Optomap Red Separation Fundus Image of Right Eye Optomap Green Separation Fundus Image

(RR29 link). See RR #29 for full details.

from magnification the sea fan FA image, is better the visualized growth of when new vessels comparing on the a timeline

avascularity surrounding the sea fan 53 sec 9 min 25 sec Rotation of the fundus image to match the orientation of the OCT

Invisible to Ophthalmoscopy Inner Retina/vitreous NFL VMT Middle Retina Exudates (in diabetes) Retinoschisis Outer Retina

evaluating the retina Yes, it is still the standard of care but SD OCT is rapidly becoming the standard of care.

17 Optomap Color Fundus Image of Right Eye Optomap Red Separation Fundus Image of Right Eye Optomap Green Separation Fundus Image of Right Eye Normal Typical retinal vascular changes in Sickle Cell Retinopathy have been presented in detail in RR #29. (RR29 link). See RR #29 for full details. Optomap Color Composite and Fluorescein Angiography Image Comparisons of Right Eye Initial Image 12 sec Leakage At a higher from magnification the sea fan FA image, is better the visualized growth of when new vessels comparing on the a timeline surface of is FA more images. apparent Note than the it is dark on the areas color of capillary image. avascularity surrounding the sea fan 53 sec 9 min 25 sec Rotation of the fundus image to match the orientation of the OCT section Note the web of new vessels (red arrows) extending from the disc into the vitreous. Invisible to Ophthalmoscopy Inner Retina/vitreous NFL VMT Middle Retina Exudates (in diabetes) Retinoschisis Outer Retina Photoreceptors () Early drusen Early choroidal neovascularization Early macula holes Ophthalmoscopy is really a gross way of evaluating the retina Yes, it is still the standard of care but SD OCT is rapidly becoming the standard of care. OCT is already the standard for retinal specialists. Best is both! With OCT, myriad disorders in numerous patients can be diagnosed years earlier than with ophthalmoscopy. In many disorders, earlier detection leads to better outcomes. Early detection of treatable diseases decrease the risk of malpractice litigation. 17

18 Invisible to Ophthalmoscopy: Plaquenil Toxicity Review s RETINA REVEALED Weekly Cases- Abnormal Normal Early Plaquenil Toxicity OD Invisible to Ophthalmoscopy: RP in 10 Year Old Black Male Abnormal Normal OS Jerome Sherman, OD

Objective Assessment of Macula and Optic Nerve

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,