When the OCT Doesn't Match the Visual Field

9/13/2019

When the OCT Doesn’t Financial disclosures Match the Visual Field Harvard Foundation Grant Teresa C. Chen, MD (Fidelity Charitable Fund) Associate Professor of Ophthalmology Harvard Medical School Department of Defense SBIR Glaucoma Service Massachusetts Eye and Ear Infirmary

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? Have not found the Holy Grail of testing FOUR STEP PLAN: 1. BAD DATA 2. GOOD DATA – NOT GLAUCOMA 3. GOOD DATA – GLAUCOMA 4. REPEAT THE TEST HVF  normal noise  testing artifacts OCT

100%  normal noise accuracy  testing artifacts

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Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? FOUR STEP PLAN: FOUR STEP PLAN: 1. BAD DATA 1. BAD DATA Artifacts to look out for: 2. GOOD DATA – NOT GLAUCOMA Reliability indices: 2. GOOD DATA – NOT GLAUCOMA  rim artifacts  3. GOOD DATA – GLAUCOMA Fixation losses 3. GOOD DATA – GLAUCOMA  lid artifacts 4. REPEAT THE TEST  False positives 4. REPEAT THE TEST 33%  wrong lens (see below)… HVF  False negatives HVF  normal noise  normal noise  testing artifacts 67 µm 69 µm 65 µm  5.7 to 7.0 dB (90% CI for normals)  OHTS: 86% of HVF abnormalities OCT not replicated on re-testing  normal noise variability is worse in glaucoma vs. normal patients  testing artifacts variability is worse as the glaucoma gets worse more false negatives as the glaucoma gets worse HVF is “noisier” than OCT

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Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? FOUR STEP PLAN: FOUR STEP PLAN: 1. BAD DATA 1. BAD DATA 2. GOOD DATA – NOT GLAUCOMA 2. GOOD DATA – NOT GLAUCOMA normal variability (same machine): normal variability (same machine): 3. GOOD DATA – GLAUCOMA 3. GOOD DATA – GLAUCOMA  RNFL - up to 4 microns  RNFL - up to 4 microns 4. REPEAT THE TEST 4. REPEAT THE TEST HVF  optic nerve rim - up to 12 microns HVF  optic nerve rim - up to 12 microns  macula (GCC) – up to 3 microns  macula (GCC) – up to 3 microns  normal noise  normal noise noise  testing artifacts  testing artifacts ~ 5µm or more normal variability (different machine): OCT OCT  RNFL - up to 14 microns progression  normal noise ~ 13µm or more  normal noise  testing artifacts  testing artifacts Expected normal values: 112.8± 13.2 110.1 ± 12.8 98.7 ± 10.9 106.6 ± 12.8 ~ 4µm or more RTVue Stratus Cirrus Spectralis

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? FOUR STEP PLAN: FOUR STEP PLAN: 1. BAD DATA 1. BAD DATA  poor signal strength 2. GOOD DATA – NOT GLAUCOMA  incorrect segmentation normal variability (same machine): 3. GOOD DATA – GLAUCOMA  missing parts of scan  RNFL - up to 4 microns 4. REPEAT THE TEST HVF  optic nerve rim - up to 12 microns HVF  macula (GCC) – up to 3 microns  normal noise  normal noise RNFL optic nerve macula  testing artifacts  testing artifacts normal variability (different machine): OCT  RNFL - up to 14 microns OCT 19.9% to 46.3% 12% - 56.5% 28.2% - 90.9%  normal noise  normal noise  testing artifacts variability is worse as the disease gets worse  testing artifacts variability is worse for sector than for global values variability is worse when you try to upgrade & change machines

 noise/variability  noise/variability  artifacts  artifacts

Normal variability is  86% HVFs not repeatable THE primary source of  86% HVFs not repeatable  46% to 91% OCT artifacts structural functional  46% to 91% OCT artifacts discordance Ashimatey BS, et al. IOVS 2016;57:502-507. Suda K, et al. Scientific Reports 2018 (8):17158.

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Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? FOUR STEP PLAN: FOUR STEP PLAN: Remember that glaucoma patients can have other diseases 1. BAD DATA 1. BAD DATA 2. GOOD DATA - NOT GLAUCOMA 2. GOOD DATA - NOT GLAUCOMA glaucoma lexicon 3. GOOD DATA – NOT GLAUCOMA 4. GOOD DATA – GLAUCOMA

5. REPEAT THE TEST nasal step temporal wedge arcuate paracentral non-glaucoma lexicon Remember that glaucoma patients can paracentral arcuate temporal sparing end stage have other diseases enlarged blind spot homonymous hemianopsia • optic nerve drusen bitemporal hemianopsia central scotoma • ischemic optic neuropathy • new retina lesions

centrocecal scotoma “spiraling” fields • CNS tumors • myopia, etc.… Pictures from Broadway DC. CEH Journal 2013.

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? Diagnosis – FOUR STEP PLAN: FOUR STEP PLAN: which is 1. BAD DATA 1. BAD DATA the outlier HVF is the outlier in… 2. GOOD DATA - NOT GLAUCOMA 2. GOOD DATA - NOT GLAUCOMA 3. GOOD DATA - GLAUCOMA 3. GOOD DATA - GLAUCOMA pre-perimetric glaucoma

From Glaucoma: A Colour Manual of Diagnosis and Treatment by Salmon and Kanski Suda K, Akagi T, Nakanishi H, et al. Evaluation of Structure-Function Relationships in Longitudinal Changes of Glaucoma Using the Spectralis OCT Follow-up Mode. Scientific Reports 2018 (8):17158.

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? Embrace mismatch as natural and common… Diagnosis – Embrace mismatch as natural and common… Diagnosis – FOUR STEP PLAN: which is FOUR STEP PLAN: which is 1. BAD DATA the outlier 1. BAD DATA the outlier 2. GOOD DATA - NOT GLAUCOMA 2. GOOD DATA - NOT GLAUCOMA Progression – Progression – 3. GOOD DATA - GLAUCOMA tests progress at 3. GOOD DATA - GLAUCOMA tests progress at 4. GOOD DATA – NOT GLAUCOMA different times 4. GOOD DATA – NOT GLAUCOMA different times 5. GOOD DATA – GLAUCOMA  5. GOOD DATA – GLAUCOMA 6. REPEATEARLY THE TEST STAGE GLAUCOMA Usually6. REPEAT change THE TEST in OCT before HVF but HVF can change before OCT  pre-perimetric glaucoma (similar to patients in OHTS study) For all glaucoma stages…  “progression in the green” (similar to 0.2  0.4 in OAG) Sometimes only OCT/structure changes (early disease) LATE STAGE GLAUCOMA Sometimes only HVF/function changes (late disease)  Once the 50 micron “floor” is reached, OCT can be Sometimes both OCT & HVF change “stable” and HVF can be progressing RNFL/GCC/optic nerve parameters can change at different times

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Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? Know that the OCT-HVF relationship is complicated Diagnosis – Know that HVF dB is logarithmic Diagnosis – FOUR STEP PLAN: which is FOUR STEP PLAN: which is 1. BAD DATA the outlier 1. BAD DATA the outlier 2. GOOD DATA - NOT GLAUCOMA 2. GOOD DATA - NOT GLAUCOMA Progression – Progression – 3. GOOD DATA - GLAUCOMA tests progress at 3. GOOD DATA - GLAUCOMA tests progress at different times different times

Structure- Structure- function function maps maps

OCT-HVF relationship is non-linear

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? What to do when the OCT & HVF don’t align? Diagnosis – FOUR STEP PLAN: which is FOUR STEP PLAN: 1. BAD DATA the outlier 1. BAD DATA 2. GOOD DATA - NOT GLAUCOMA 2. GOOD DATA - NOT GLAUCOMA Progression – 3. GOOD DATA - GLAUCOMA tests progress at 3. GOOD DATA - GLAUCOMA 4. GOOD DATA – NOT GLAUCOMA different times 4. REPEAT THE TEST Different5. GOOD doctors DATA – GLAUCOMA and definitions of HVF progression don’t agree…. 5. GOOD DATA – NOT GLAUCOMA Structure- 6. REPEAT THE TEST function 6. GOOD DATA – GLAUCOMA  Subjective clinical judgment maps 7. REPEAT THE TEST  AGIS, EMGT, CIGTS (i.e. 1 year earlier than AGIS) OCT-HVF  Event-based analysis relationship is non-linear  GPA derived from EMGT  Trend-based analysis Definition of progression differs

Reasons for OCT HVF mismatch Reasons for OCT HVF mismatch What to do when the OCT & HVF don’t align? FOUR STEP PLAN: What to do when the OCT & HVF don’t align? 1. BAD DATA 2. GOOD DATA - NOT GLAUCOMA 3. GOOD DATA - GLAUCOMA FOUR STEP PLAN: 4. REPEAT THE TEST 1. BAD DATA HVF – referred for progression HVF – when repeated 2. GOOD DATA - NOT GLAUCOMA 3. GOOD DATA - GLAUCOMA 4. REPEAT THE TEST – back to baseline …inter-test fluctuation can look like glaucoma progression.

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T THANKS Harvard Foundation Grant (Fidelity Charitable Fund) National Institutes of Health - RO1 EY14975-01 Harvard Catalyst H American Glaucoma Society Mid-Career Award Massachusetts Lions Eye Research Fund, Inc. Department of Defense SBIR A Massachusetts General Hospital Massachusetts Eye and Ear and VU University • Kayoung Yi, MD, PhD • Edem Tsikata, PhD • Johannes de Boer, PhD • Alice Vercellin Verticchio, MD • B. Hyle Park, PhD • John B. Miller, MD • Mircea Mujat, PhD N • Iryna Falkenstein, MD • Vivek Srinivasan, PhD • Linda Yi-Chieh Poon, MD • Barry Cense, PhD • Stacey Brauner, MD • Gary Tearney, PhD • Ziad Khoueir, MD K • Brett Bouma, PhD • Derrick T. Lin, MD • Mark Pierce, PhD • Daniel Deschler, MD • Wei Sun, BS • Peter A.D. Rubin, MD • Vivek Srinivasan, PhD • Mark Latina, MD