Thyroid Eye Disease Awareness and Education Webinar Tuesday, July 9, 2019
Welcome Panelists Babak Larian, MD Raymond S. Douglas, MD, PhD Christina Seeden Assistant Clinical Professor of Surgery, Advocate Director of Orbital and Thyroid Eye Division of Head and Neck Surgery, UCLA Disease Program David Geffen School of Medicine Cedars-Sinai Medical Center in Los Director, Head and Neck Cancer Center Angeles and Head and Neck Tumor Board, Cedar- Sinai Medical Center
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
T HYROID EYE DISEASE : WHAT IS IT AND HOW TO TREAT IT .. R AYMOND S. D OUGLAS MD P H D P ROFESSOR OF S URGERY D IVISION OF O PHTHALMOLOGY 150 N ORTH R OBERSTON S UTIE 314 B EVERLY H ILLS CA I NFO @ RAYMONDDOUGLASMD . COM
“The speaker declares no current financial conflicts of interest”
W HAT IS T HYROID E YE D ISEASE ?
The Three Components of Graves’ Disease
Heterogeneous disease
Active Phase Disease Stable Phase Ideal Surgery Immunomodulatory Therapy 5-7years 18-36 months Time
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
IGF-1R Inhibition Can Attenuate TSHR Signaling Teprotumumab Phase 2 IGF-1R Antagonist Inhibition of IGF-1R with a mAb R AYMOND S. D OUGLAS MD P H D antagonist has potential to P RINCIPAL I NVESTIGATOR block pathological autoantigen 22 U S AND I NTERNATIONAL C ENTERS signaling through both IGF-1R Tsui et al J Immunology 181:4397 (2008) and TSHR
Graves’ Orbitopathy: Disease Time Course Active Phase Stable Phase Disease Activity Untreated Teprotumumab Efficacious therapy 3 6 years 1.5 2 Smith & Douglas (2011)
24-week randomized, double-masked, placebo- controlled treatment trial of Teprotumumab Teprotumumab Active Randomization Infusions q3w TED Screening (total of 8) Off Treatme eatment 18 to 75 years Follow Up Period < 9 mo. since active TED Placebo onset with no prior Infusions q3w treatment ǂ (total of 8) CAS ≥ 4 FT4 and FT3 <50% above or 48 weeks 24 weeks below normal limits Week 24 assessment was Week 72 assessment was 3 weeks after last dose 51 weeks after last dose ǂ Excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolon e 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. 18
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
Clinical Activity Score Smith TJ et al. N Engl J Med 2017;376:1748-1761
Proptosis Reduction Smith TJ et al. N Engl J Med 2017;376:1748-1761
Individual Patient Plots (week 24) 22
Smith TJ et al. N Engl J Med 2017;376:1748-1761
Pre treatment Week 24 control
Teprotumumab Week 24 Pre treatment
Results • Teprotumumab, an antibody to the insulin- like growth factor I receptor, led to significant responses in 69% of patients with decreased proptosis (intent to treat). • 79% of patients (data available) had a decreased proptosis and response to Teprotumumab • Proptosis reduction was >2.5 mm • Worse disease bigger effect • May replace surgery
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 Single Stage Reconstruction It IS about how many surgeries and downtime
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
Decompression and OML release- No eyelid surgery 40
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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 August 2007 October 2006 August 2012 August 2011 Diagnosed with Graves Before RAI
Christina’s TED Journey Before TED 2011 Active TED 2012 Active TED 2012 1 month after surgery
Christina’s TED Journey February 2013 August 2013 Befo fore surger gery 3.5 months nths after ter surge gery ry
Christina’s TED Journey February 2013 Now
Thank You Panelists Babak Larian, MD Raymond S. Douglas, MD, PhD Christina Seeden Assistant Clinical Professor of Surgery, Advocate Director of Orbital and Thyroid Eye Division of Head and Neck Surgery, UCLA Disease Program David Geffen School of Medicine Cedars-Sinai Medical Center in Los Director, Head and Neck Cancer Center Angeles and Head and Neck Tumor Board, Cedar- Sinai Medical Center
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