Thyroid Eye Disease Awareness
and Education Webinar
Tuesday, July 9, 2019
Welcome Panelists
Babak Larian, MD
Assistant Clinical Professor of Surgery, Division of Head and Neck Surgery, UCLA
David Geffen School of Medicine
Director, Head and Neck Cancer Center and Head and Neck Tumor Board, Cedar-
Sinai Medical Center
Raymond S. Douglas, MD, PhD
Director of Orbital and Thyroid Eye Disease Program
Cedars-Sinai Medical Center in Los Angeles
Christina Seeden
Advocate
Babak Larian, MD
Assistant Clinical Professor of Surgery, Division of
Head and Neck Surgery, UCLA David Geffen School of
Medicine
Director, Head and Neck Cancer Center and Head and
Neck Tumor Board, Cedar-Sinai Medical Center
Raymond S. Douglas, MD, PhD
Director of Orbital and Thyroid Eye Disease Program
Cedars-Sinai Medical Center in Los Angeles
THYROID EYE DISEASE: WHAT IS IT AND
HOW TO TREAT IT..
RAYMOND S. DOUGLAS MD PHD
PROFESSOR OF SURGERY
DIVISION OF OPHTHALMOLOGY
150 NORTH ROBERSTON SUTIE 314
BEVERLY HILLS CA
“The speaker declares no current financial
conflicts of interest”
WHAT IS THYROID EYE DISEASE ?
The Three Components of Graves’ Disease
Heterogeneous disease
Dis
ea
se
Time
Ideal
Immunomodulatory
Therapy
Active Phase
Stable Phase
18-36 months 5-7years
Surgery
Thyroid Eye Disease
Autoimmune inflammatory disease
often with extensive fibrosis
Permanent Facial disfigurement
No treatment to prevent disfigurement
“Standard of Care” watch and wait - then surgery
What about TED specific therapy ???
Heterogeneous disease
Delineate the common molecular mechanisms
Tsui et al J Immunology 181:4397 (2008)
IGF-1R Inhibition Can
Attenuate TSHR Signaling
Inhibition of IGF-1R with a mAb antagonist has potential to block pathological autoantigen signaling through both IGF-1R and TSHR
Teprotumumab Phase 2 IGF-1R Antagonist
RAYMOND S. DOUGLAS MD PHD
PRINCIPAL INVESTIGATOR
22 US AND INTERNATIONAL CENTERS
Graves’ Orbitopathy:
Disease Time CourseD
isease A
ctivity
Active Phase Stable Phase
1.5 2 3 6 years
Untreated
Smith & Douglas (2011)
Teprotumumab Efficacious
therapy
18
24-week randomized, double-masked, placebo-
controlled treatment trial of Teprotumumab
ǂ Excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent. There must be at least 6 weeks between last administration of steroids and study
randomization. *No additional treatment during at least the first 3 months unless medically indicated. i.e. decompression. Elective treatments should be avoided during the first 3 months of the follow up period.
Active
TED 18 to 75 years
< 9 mo. since active TED
onset with no prior
treatmentǂ
CAS ≥ 4
FT4 and FT3 <50% above or
below normal limits
Teprotumumab
Infusions q3w
(total of 8)
Placebo
Infusions q3w
(total of 8)
Sc
ree
nin
g
Ra
nd
om
iza
tio
n
Off Treatment
Follow Up Period
Week 24 assessment was
3 weeks after last dose
Week 72 assessment was
51 weeks after last dose
24 weeks 48 weeks
Study Design
•Less than 9 months since TED diagnosis
•Moderate – Severe disease
•CAS 4 or greater
Endpoints•Proptosis reduced by 2 mm
•Study designed to Medically REPLACE SURGERY
Smith TJ et al. N Engl J Med 2017;376:1748-1761
Clinical Activity Score
Smith TJ et al. N Engl J Med 2017;376:1748-1761
Proptosis Reduction
Individual Patient Plots (week 24)
22
Smith TJ et al. N Engl J Med 2017;376:1748-1761
Pre treatment
Week 24
control
Pre treatment
Teprotumumab
Week 24
• Teprotumumab, an antibody to the insulin-like growth factor I receptor, led to significant responses in 69% of patientswith decreased proptosis (intent to treat).
• 79% of patients (data available) had a decreased proptosis and response toTeprotumumab
• Proptosis reduction was >2.5 mm• Worse disease bigger effect• May replace surgery
Results
Single Stage Approach to Orbital
Decompression
Adequate decompression can dramatically
reduce need for eyelid surgery
Less than 5% need lower eyelid surgery
Aesthetic Functional Reconstruction
It IS about how we Look and Feel
It IS about how many surgeries and downtime
Single Stage Reconstruction
What is “aesthetic-functional”
reconstruction?
Form follows function
• Goal: Return to (Improve upon) pre disease appearance and function
Key Factors to Customized Surgical
Planning
• Patient Goals
• Type of disease fat vs muscle- Risk profile
• Disease severity
• Presence/risk of double vision
• Bony structure (bone available for decompression)
• Soft tissue structure
• Aesthetic contour of brow, eyelids, midface
Fat + Lateral/Superior Decompression
6mm proptosis
reduction, no
additional surgery
Natural lower eyelid appearance
Done by customizing decompression technique not
additional surgery
Normal Eyelid contour restored after decompression
Fat + Lateral Decompression
3-4 mm proptosis
reduction
Fat + Lateral / Superior Decompression
6mm proptosis
reduction
Improve Cheek junction
During decompression
Eyelid rectrator release
Orbitomalar ligament release
Midface lift / support
Cheek implants
40
Decompression and OML release-No eyelid surgery
42
43
44
Summary
• Orbital And Oculoplastic Surgery Service
• Available 24/7 consults
• Thyroid Eye Disease Program
• Research
• Integrated Multidisciplinary Clinical Care
• Financial Assistance Program from philanthropy
Christina’s Thyroid Eye Disease
Journey
Christina’s TED Journey
October 2006Diagnosed with Graves
August 2007 August 2011Before RAI
August 2012
Christina’s TED Journey
Before TED 2011 Active TED 2012 Active TED 2012 1 month after surgery
Christina’s TED JourneyFebruary 2013Before surgery
August 20133.5 months after surgery
Christina’s TED JourneyFebruary 2013 Now
Thank You Panelists
Babak Larian, MD
Assistant Clinical Professor of Surgery, Division of Head and Neck Surgery, UCLA
David Geffen School of Medicine
Director, Head and Neck Cancer Center and Head and Neck Tumor Board, Cedar-
Sinai Medical Center
Raymond S. Douglas, MD, PhD
Director of Orbital and Thyroid Eye Disease Program
Cedars-Sinai Medical Center in Los Angeles
Christina Seeden
Advocate