how is amd imaged? how: amd imaging · fundus autofluorescence peripheral faf findings seen in both...

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1 Cole Eye Institute Cole Eye Institute Update On Imaging For AMD Rishi P. Singh Assistant Professor Of Ophthalmology Medical Director, Clinical Systems Office Staff Physician, Cleveland Clinic Rishi P. Singh Assistant Professor Of Ophthalmology Medical Director, Clinical Systems Office Staff Physician, Cleveland Clinic Cole Eye Institute Cole Eye Institute Agenda Discuss the imaging modalities routinely used and their role Highlight particular OCT enhancements which aide in the management of AMD patients Discuss some of the imaging findings from recent clinical trials Discuss the imaging modalities routinely used and their role Highlight particular OCT enhancements which aide in the management of AMD patients Discuss some of the imaging findings from recent clinical trials Cole Eye Institute Cole Eye Institute How is AMD Imaged? Cole Eye Institute Cole Eye Institute How: AMD Imaging

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Page 1: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

1

Cole Eye InstituteCole Eye Institute

Update On Imaging For AMD

Rishi P. Singh

Assistant Professor Of Ophthalmology

Medical Director, Clinical Systems Office

Staff Physician, Cleveland Clinic

Rishi P. Singh

Assistant Professor Of Ophthalmology

Medical Director, Clinical Systems Office

Staff Physician, Cleveland Clinic

Cole Eye InstituteCole Eye Institute

Agenda

● Discuss the imaging modalities routinely used and their role

● Highlight particular OCT enhancements which aide in the management of AMD patients

● Discuss some of the imaging findings from recent clinical trials

● Discuss the imaging modalities routinely used and their role

● Highlight particular OCT enhancements which aide in the management of AMD patients

● Discuss some of the imaging findings from recent clinical trials

Cole Eye InstituteCole Eye Institute

How is AMD Imaged?

Cole Eye InstituteCole Eye Institute

How: AMD Imaging

Page 2: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

2

Cole Eye InstituteCole Eye Institute

Color Fundus Photography

● Role is uncertain except when interpreting FA

● Documenting activity such as hemorrhage may be useful to follow the patient

● Identification of fibrosis usually an exclusion for clinical trials

● Future ‘anti-fibrotic’ therapies may increase the relevance

● Role is uncertain except when interpreting FA

● Documenting activity such as hemorrhage may be useful to follow the patient

● Identification of fibrosis usually an exclusion for clinical trials

● Future ‘anti-fibrotic’ therapies may increase the relevance

Cole Eye InstituteCole Eye Institute

How: AMD Imaging

Cole Eye InstituteCole Eye Institute

Fundus Autofluorescence

● FAF in AMD mainly used for tracking GA

● Helps explain to patients – Dark is Bad

● FAF in AMD mainly used for tracking GA

● Helps explain to patients – Dark is Bad

Cole Eye InstituteCole Eye Institute

Measuring Geographic Atrophy with RPE Subillumination -Correlation between OCT and FAF

• Comparison of areas designated as sub-RPE Illumination by the CIRRUS HD-OCT versus those designated as Geographic Atrophy on fundus autofluorescence (FAF).

• Strong correlation was found between the two modalities

• Comparison of areas designated as sub-RPE Illumination by the CIRRUS HD-OCT versus those designated as Geographic Atrophy on fundus autofluorescence (FAF).

• Strong correlation was found between the two modalities

Spectral domain optical coherence tomographic imaging of geographic atrophy.Lujan BJ, Rosenfeld PJ, Gregori G, Wang F, Knighton RW, Feuer WJ, Puliafito CA.Ophthalmic Surg Lasers Imaging. 2009 Mar-Apr;40(2):96-101.

Page 3: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

3

Cole Eye InstituteCole Eye Institute

Fundus Autofluorescence

● Peripheral FAF findings seen in both neovascularand non neovascular AMD – 68.9% abnormal

● Classification

● Granular

● Nummular

● Mottled

● Peripheral FAF findings seen in both neovascularand non neovascular AMD – 68.9% abnormal

● Classification

● Granular

● Nummular

● Mottled

Colin S. Tan , Florian Heussen , SriniVas R. Sadda

Peripheral Autofluorescence and Clinical Findings in Neovascular and Non-neovascular Age-related Macular Degeneration

Ophthalmology, Volume 120, Issue 6, 2013, 1271 - 1277Cole Eye InstituteCole Eye Institute

How: AMD Imaging

Cole Eye InstituteCole Eye Institute

Fluorescein Angiography - Baseline

Cole Eye InstituteCole Eye Institute

Fluorescein Angiography

Page 4: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Fluorescein Angiography – Follow-up

Cole Eye InstituteCole Eye Institute

When: Fluorescein Angiography – Follow-up

Cole Eye InstituteCole Eye Institute

Fluorescein Angiography – Follow-up

Cole Eye InstituteCole Eye Institute

How: AMD Imaging

Page 5: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

5

Cole Eye InstituteCole Eye Institute

Indocyanine Green Angiography:

Cole Eye InstituteCole Eye Institute

Indocyanine Green Angiography

Cole Eye InstituteCole Eye Institute

How: AMD Imaging

Cole Eye InstituteCole Eye Institute

OCT Treatment Monitoring

Page 6: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Improved acquisition times and more data:Time Domain vs Spectral Domain

Scanning strategies

512 X 6 = 3072 A-scans(7.7 seconds)

200 X 200 = 40,000 A-scans512 X 128 = 65,536 A-scans4096 X 5 = 20,480 A-scansTotal A-scans = 126,016 A-scans(4.7 seconds)

Cole Eye InstituteCole Eye Institute

How is a cube scan made?

Axial scans (A-scans) make up a B-Scan

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40,000 A-scans in 1.5 seconds

6mm

2mm

B-scans make up the 3-D dataset or SDOCT cube

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The benefit of more B-scans

● An increase in the number of B-scans reduces the variability of measuring the central subfield thickness and macular volume.

● An increase in the number of B-scans reduces the variability of measuring the central subfield thickness and macular volume.

Page 7: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Applications for the cube scan

SDOCT Cube

Sub‐RPE Illumination Prior Current Difference % Change

Area in 5 mm Circle (mm2) 10.2 12.1 1.90               18.6%

Closest distance to Fovea (mm) 0.6 0.0 ‐0.60 ‐100.0%

RPE Elevations Prior Current Difference % Change

Area in 3 mm Circle (mm2) 3.2 3.9 0.7 21.9%

Area in 5 mm Circle (mm2) 3.7 4.7 1.0 27.0%

Volume in 3 mm Circle (mm3) 0.32 0.53 0.21 65.6%

Volume in 5 mm Circle (mm3) 0.34 0.58 0.24 70.6%

RPE Elevations Sub-RPE Illumination

RPS1

Cole Eye InstituteCole Eye Institute

Advanced RPE Analysis

Sub‐RPE Illumination Prior Current Difference % Change

Area in 5 mm Circle (mm2) 10.2 12.1 1.90               18.6%

Closest distance to Fovea (mm) 0.6 0.0 ‐0.60 ‐100.0%

RPE Elevations Prior Current Difference % Change

Area in 3 mm Circle (mm2) 3.2 3.9 0.7 21.9%

Area in 5 mm Circle (mm2) 3.7 4.7 1.0 27.0%

Volume in 3 mm Circle (mm3) 0.32 0.53 0.21 65.6%

Volume in 5 mm Circle (mm3) 0.34 0.58 0.24 70.6%

RPE Elevations Sub-RPE Illumination

Cole Eye InstituteCole Eye Institute

Advanced RPE AnalysisScreen 1

Cole Eye InstituteCole Eye Institute

Advanced RPE AnalysisScreen 2

Page 8: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

Slide 25

RPS1 Cube scan only, not the picutre to the left. Rishi Singh, 8/21/2013

Page 9: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Measuring Geographic Atrophy with RPE Subillumination -Correlation between OCT and FAF

• Comparison of areas designated as sub-RPE Illumination by the CIRRUS HD-OCT versus those designated as Geographic Atrophy on fundus autofluorescence (FAF).

• Strong correlation was found between the two modalities

• Comparison of areas designated as sub-RPE Illumination by the CIRRUS HD-OCT versus those designated as Geographic Atrophy on fundus autofluorescence (FAF).

• Strong correlation was found between the two modalities

Spectral domain optical coherence tomographic imaging of geographic atrophy.Lujan BJ, Rosenfeld PJ, Gregori G, Wang F, Knighton RW, Feuer WJ, Puliafito CA.Ophthalmic Surg Lasers Imaging. 2009 Mar-Apr;40(2):96-101.

Cole Eye InstituteCole Eye Institute

Case example – RPE elevation analysis

● 63 y/o woman with neovascular AMD

● Decreased vision for 2 months, 20/100

● 63 y/o woman with neovascular AMD

● Decreased vision for 2 months, 20/100

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Area: 14.896 mm2

Volume: 7.242 mm3

Intravitreal Lucentis Injected

Page 10: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

BaselineVA: 20/1007.242 mm3

Lucentis #1

1 m s/p L #1VA: 20/402.031 mm3

Lucentis #2

1 m s/p L #2VA: 20/301.472 mm3

Lucentis #3

Area: 15 mm2→13 mm2 (-13%)Volume: 7.2 mm3 →1.5 mm3 (-79%)

Case example – RPE elevation analysis

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OCT Artifacts

● Not uncommon even with SDOCT

● Can affect both quantitative and qualitative interpretations

● Artifacts can result from

● Software errors

● Patient factors

● User errors

● Not uncommon even with SDOCT

● Can affect both quantitative and qualitative interpretations

● Artifacts can result from

● Software errors

● Patient factors

● User errors

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Most common artifacts seen

● Misalignment

● Blink or motion

● Shadowing

● Software error

● Misalignment

● Blink or motion

● Shadowing

● Software error

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Automatic Fovea Finder

• OCT software identifies the fovea location automatically by finding the reduced reflectivity below the retina.

• OCT software identifies the fovea location automatically by finding the reduced reflectivity below the retina.

Page 11: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Macula Thickness Report

• Fully automated analysis

• Fovea Finder™ automates ETDRS grid placement

• Layer maps highlight abnormalities

• Normative data

• Fully automated analysis

• Fovea Finder™ automates ETDRS grid placement

• Layer maps highlight abnormalities

• Normative data

Cole Eye InstituteCole Eye Institute

Case Example – Fovea Finder

OSODMacula Thickness : Macular Cube 512x128

Normativedata is notavailable.Patient age< 18.

Overlay: ILM - RPE Transparency: 50 %

ILM-RPE Thickness (µm)

ILM - RPE

ILM

RPE

28410.2319ILM - RPE

CubeAverage

Thickness(µm)

CubeVolume(mm³)

CentralSubfield

Thickness(µm)

Fovea: Not found

OSODMacula Thickness : Macular Cube 512x128

Normativedata is notavailable.Patient age< 18.

Overlay: ILM - RPE Transparency: 50 %

ILM-RPE Thickness (µm)

ILM - RPE

ILM

RPE

2759.9259ILM - RPE

CubeAverage

Thickness(µm)

CubeVolume(mm³)

CentralSubfield

Thickness(µm)

Fovea: 294, 67

Fovea Finder OFFCentral subfield = 319

Fovea Finder ONCentral subfield = 259

Cole Eye InstituteCole Eye Institute

Eye Tracking Software

● Allows for improved image acquisition in cases of patient cooperation and eye movement.

● Improves registration capabilities

● Allows for improved image acquisition in cases of patient cooperation and eye movement.

● Improves registration capabilities

Cole Eye InstituteCole Eye Institute

Case Example

Good cooperationNo Fast Trac

Patient blinkingFast Trac OFF

Patient blinkingFast Trac ON

Page 12: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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● Enhanced Depth Imaging

● Improves visualization of the choroid

● Enhanced understanding of disease pathophysiology

● Various protocols based on device utilized

● Enhanced Depth Imaging

● Improves visualization of the choroid

● Enhanced understanding of disease pathophysiology

● Various protocols based on device utilized

EDI‐OCT:  Imaging the Choroid

Cole Eye InstituteCole Eye Institute

Outer Retinal Tubulation (ORT)

● Preservation of photoreceptors

● Loss of outer segment interdigitation with RPE

● Disconnect from lateral photoreceptors

● Preservation of photoreceptors

● Loss of outer segment interdigitation with RPE

● Disconnect from lateral photoreceptors

Cole Eye InstituteCole Eye Institute

CNV

CNV

May not indicate neovascular activity

Outer Retinal Tubulation (ORT)

Cole Eye InstituteCole Eye Institute

Outer Retinal Tubulation

(ORT)

Curved C-scan Imaging

Cirrus

Page 13: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Why does this all matter?

Cole Eye InstituteCole Eye Institute

Comparison of AMD Treatments Trials (CATT): Anatomic Results

Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health,

DHHS

Supported by Cooperative Agreements from the National Eye Institute, National Institutes of Health,

DHHS46

Cole Eye InstituteCole Eye Institute

-250

-200

-150

-100

-50

0

0 4 8 12 16 20 24 28 32 36 40 44 48 52

Lucentis Monthly

Avastin Monthly

Lucentis PRN

Avastin PRN

47

All Groups

Mean Change in Total Retinal Thickness Over Time

µm

Week

-168-164-152

-196

Cole Eye InstituteCole Eye Institute

OCT of Typical Eye at Baseline

460u

Page 14: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Lucentis Monthly Thinner Than Normal

Lucentis Monthly Avastin Monthly Lucentis PRN Avastin PRN

Baseline 251u 254u 247u 252u

Week 52 152u 172u 166u 173u

Lucentis Monthly Avastin Monthly Lucentis PRN Avastin PRN

Baseline 251u 254u 247u 252u

Week 52 152u 172u 166u 173u

49 Cole Eye InstituteCole Eye Institute50

Percent with No Fluid at 1 Year

43.7%

26.0% 23.9%19.2%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Pe

rce

nta

ge

of

Pa

tie

nts

Lucentis Monthly (n=284)

Avastin Monthly (n=265)

Lucentis PRN (n=285)

Avastin PRN (n=271) P < 0.001

Cole Eye InstituteCole Eye Institute

Residual Fluid

Small amounts of residual fluid have minimal effect on VA

unless intraretinal and in center of fovea

Small amounts of residual fluid have minimal effect on VA

unless intraretinal and in center of fovea

51

Jaffe GJ, Martin DF, Toth CA, et al. Macular morphology and visual acuity in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Ophthalmology 2013

Cole Eye InstituteCole Eye Institute

SD-OCT vs TD-OCT

Page 15: How is AMD Imaged? How: AMD Imaging · Fundus Autofluorescence Peripheral FAF findings seen in both neovascular and non neovascular AMD – 68.9% abnormal Classification Granular

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Cole Eye InstituteCole Eye Institute

Discrepant Treatment?

● Reading Center says fluid: no Rx

● Reading Center says no fluid: yes Rx

● Reading Center says fluid: no Rx

● Reading Center says no fluid: yes Rx

53 Cole Eye InstituteCole Eye Institute

Discrepant Treatment

● Lucentis PRN 29%

● Avastin PRN 25%

● Lucentis PRN 29%

● Avastin PRN 25%

54

Cole Eye InstituteCole Eye Institute

Conclusions

● Multiple modalities to pick from for imaging AMD

● Each has their own role

● Fundus – research, correlating angiography

● AF – patient education, dry AMD progression

● FA – Initially and only in cases of poor response

● ICG – Only in cases of poor response

● OCT – every visit, still limitations of technology

● Multiple modalities to pick from for imaging AMD

● Each has their own role

● Fundus – research, correlating angiography

● AF – patient education, dry AMD progression

● FA – Initially and only in cases of poor response

● ICG – Only in cases of poor response

● OCT – every visit, still limitations of technology

Cole Eye InstituteCole Eye Institute

Conclusions

● Variety of OCT technologies have increased our ability to care for AMD patients

● Eye Tracking

● Fovea finder

● Sub RPE illumination and RPE depression

● Higher resolution to find fluid and pathology

● Despite this, outcomes with TDOCT were good.

● Intraretinal fluid with in the fovea was the biggest predictor of acuity

● Variety of OCT technologies have increased our ability to care for AMD patients

● Eye Tracking

● Fovea finder

● Sub RPE illumination and RPE depression

● Higher resolution to find fluid and pathology

● Despite this, outcomes with TDOCT were good.

● Intraretinal fluid with in the fovea was the biggest predictor of acuity