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Группа авторов. Graves' Orbitopathy
Graves’ Orbitopathy. A Multidisciplinary Approach – Questions and Answers
Graves’ Orbitopathy. A Multidisciplinary Approach – Questions and Answers
Contents
Preface to the Third, Revised and Expanded Edition
Preface to the Second, Revised Edition
Preface to the First Edition
Clinical Manifestations
What Are the Common Signs and Symptoms of Early Graves’ Orbitopathy?
What Are Other Signs and Symptoms of Graves’ Orbitopathy?
What Signs Should Question the Diagnosis of Graves’ Orbitopathy?
Are There Racial Differences in How Graves’ Orbitopathy Manifests?
Is the Presentation of Graves’ Orbitopathy Different in Older Compared to Younger Patients?
Why Can the Clinical Presentation of Graves’ Orbitopathy Be So Variable?
Can You Give Me a Short Mechanistic Explanation for All These Clinical Manifestations?
What Do the Terms “Activity” and “Severity” Denote?
Why Is It Important to Distinguish Activity and Severity when Evaluating Patients?
What Signs and Symptoms Are Valuable for Assessing Activity?
How Are These Signs Assessed?
Eyelid Swelling
Eyelid Erythema
Conjunctival Redness
Chemosis (Conjunctival Oedema)
Inflammation of the Caruncle or Plica
How Reproducible Are These Assessments?
What Value Does the “Clinical Activity Score” Have?
Do Patients without Signs of Activity Ever Have Active Disease?
What Should I Do if I Am Not Sure whether the Disease Is Active?
Are There Any Other Ways to Evaluate Activity other than Clinical Examination?
When Should These Other Methods for Assessing Activity Be Used in Routine Clinical Practice?
What Signs Are Helpful for Assessing Severity?
What Value Does the Mnemonic “NOSPECS” Have?
How Are Signs of Severity Assessed?
How Reproducible Are These Assessments?
How Is Severity Best Classified?
How Do You Decide whether a Patient Has Dysthyroid Optic Neuropathy?
Can Dysthyroid Optic Neuropathy Ever Be Present with Normal Vision?
Are Some Patients at Particular Risk?
What Other Assessments Are Useful in Evaluating Possible Dysthyroid Optic Neuropathy?
Should These Tests Be Performed in All Patients at Every Assessment?
Are There Any Other Assessment Systems in Common Use?
References
Orbit-Thyroid Relationship
Should This Condition Always Be Called Graves’ Orbitopathy?
Is Graves’ Orbitopathy Exclusively Occurring in Patients with Graves’ Hyperthyroidism?
Do All Patients with Graves’ Hyperthyroidism Have Graves’ Orbitopathy?
Are There Any Relationships between Hyperthyroidism, Hypothyroidism, and Graves’ Orbitopathy?
Is Graves’ Orbitopathy Related to Thyroid Autoimmunity?
Are There Other Extrathyroidal Manifestations of Graves’ Disease apart from Graves’ Orbitopathy?
References
Epidemiology
What Is the Estimated Incidence and Prevalence of Graves’ Orbitopathy?
Has the Occurrence of Graves’ Orbitopathy Changed over the Last Few Decades?
Is the Age and Sex Distribution of Graves’ Orbitopathy Similar to That of Graves’ Hyperthyroidism?
Are There Ethnic Differences?
What Are the Risk Factors for the Occurrence of Graves’ Orbitopathy?
Can Particular Drugs Trigger or Modify Graves’ Orbitopathy and Its Course?
Is Tobacco Bad for Graves’ Orbitopathy?
Has Nutrition an Effect on Graves’ Orbitopathy?
Does Total Thyroidectomy for Other Diseases than Graves’ Disease Preclude the Development of Graves’ Orbitopathy?
References
Pathogenesis
What Are the Pathological Changes in Orbital Tissue in Graves’ Orbitopathy?
Early Inflammatory Changes
De novo Adipogenesis
Increased Production of Glycosaminoglycans
How Do the Pathological Changes Give Rise to the Clinical Manifestations?
What Triggers Graves’ Orbitopathy?
Is Graves’ Orbitopathy Triggered by an Autoimmune Phenomenon? If So, What Is the Nature of the Autoantigen?
Why Is the Orbit Special and a Target for Thyroid Autoimmunity?
What Kind of Immune Reactions Take Place within the Orbit?
Does Thyroid-Stimulating Hormone Receptor Activation and/or Autoreactivity to Thyroid-Stimulating Hormone Receptor Play a Role in the Onset or Development of Graves’ Orbitopathy?
Is There a Familial Predisposition or a Specific Genetic Background for Graves’ Orbitopathy?
How Do Environmental Factors Increase the Risk and Severity of Graves’ Orbitopathy?
How May These Observations and Current Understanding Lead to More Effective Treatment of Graves’ Orbitopathy?
References
Orbital Imaging
Is Orbital Imaging Always Necessary?
What Are the Relative Benefits of Orbital CT and MRI?
What Is Apical Crowding?
What Is the Place of Orbital Ultrasound?
What Lessons Can We Learn from Orbital Octreoscan?
What Other Imaging Techniques May Be Useful?
References
Diagnosis and Differential Diagnosis of Graves’ Orbitopathy
Can You Give an Overall Scheme for the Diagnosis of Graves’ Orbitopathy?
Which Clinical Findings Are Helpful in Making a Diagnosis of Graves’ Orbitopathy?
Can One Make a Diagnosis of Graves’ Orbitopathy Based on Medical History and Clinical Picture Alone?
Do We Always Need to Order Thyroid Autoantibody and Thyroid Function Tests?
Which Imaging Technique Is Best to Make a Diagnosis of Graves’ Orbitopathy, and Is Imaging Always Requested?
Which Are the Most Frequent Conditions Mimicking Graves’ Orbitopathy?
Orbital Myositis
Caroticocavernous Fistula
Immunoglobulin G4-Related Orbital Disease
Orbital Meningioma
Non-Hodgkin Lymphoma
References
Natural History
Does Graves’ Orbitopathy Occur at the Same Time as Hyperthyroidism?
Does Restoring Euthyroidism Lead to Improvement in Graves’ Orbitopathy?
What Effect May Hypothyroidism Have?
What Is the Typical Course of the Disease?
What Happens to Orbital Fat during the Course of the Disease?
What Is the Difference between Activity and Severity?
How Do You Determine Which Phase of the Disease the Patient Is Displaying?
How Does the Phase of the Disease Influence the Choice of Treatment?
Will Graves’ Orbitopathy Eventually Burn Itself Out?
Will the Orbital Changes Return to Normal when the Condition Eventually Resolves?
How Long Is It Likely to Take before the Disease Becomes Inactive?
Once the Condition Has Become Inactive (whether Treated or Untreated), Is It Likely to Flare Up Again?
Are There Any Other Factors, Additional to Thyroid Status, That May Influence the Course of the Disease?
References
General Management Plan for Graves’ Orbitopathy
Is There General Agreement among Specialists on How to Manage Graves’ Orbitopathy?
What Are the Priorities when Faced with a New Presentation of Graves’ Orbitopathy?
Should the Patient Be Informed about Risk Factors Affecting the Course of Graves’ Orbitopathy?
What Is the Evidence about the Role of Smoking on the Course of Graves’ Orbitopathy?
Does Thyroid Status Affect Graves’ Orbitopathy?
Are There Simple Measures That Can Help the Eyes?
Is Early Referral to Specialized Centres Important?
Can You Provide the Patient with an Overall Management Scheme?
References
Combined Thyroid-Eye Clinics
What Are Combined Thyroid-Eye Clinics?
Why Is a Multidisciplinary Approach Recommended?
Can Patient Support Groups Be Helpful?
I Have Heard of a Fast-Track Clinic for Graves’ Orbitopathy Patients: What Is That?
What Can I Expect when Starting a Combined Thyroid-Eye Clinic?
References
Thyroid Treatment
Do the Eyes Care How Euthyroidism Is Obtained and Maintained? Antithyroid Drugs
Radioactive Iodine
Thyroidectomy
Are There Criteria for Preferring One of the Treatment Options for Hyperthyroidism over the Others in Graves’ Orbitopathy?
Can Risk Factors Which Predict Appearance or Worsening of Graves’ Orbitopathy after Radioiodine Be Identified?
Should the Presence of Graves’ Orbitopathy Restrict Our Use of Radioiodine Therapy?
Does Avoiding Transient Hypothyroidism following Radioiodine Therapy Affect the Course of Graves’ Orbitopathy?
What Is the Role of Total Thyroid Ablation in the Management of Hyperthyroidism in Graves’ Orbitopathy?
Conclusions
References
Management of Mild Graves’ Orbitopathy
Which Parameters Should Be Taken into Account to Define a Clinically Evident Graves’ Orbitopathy as Mild?
Are Mild Forms Likely to Progress to More Severe Graves’ Orbitopathy?
Is a “Wait-and-See” Policy Justified in Patients with Mild Graves’ Orbitopathy?
Are Low-Dosage Oral Steroids Advisable or Is Orbital Radiotherapy Preferable?
What Is the Rationale for Antioxidant Therapy like Selenium in Graves’ Orbitopathy?
References
Management of Moderately Severe Graves’ Orbitopathy
How Is Moderately Severe Graves’ Orbitopathy Defined?
Is Immunosuppression Indicated in Moderately Severe Graves’ Orbitopathy?
What Are the Cellular and Molecular Mechanisms of Steroid Anti-Inflammation and Immunosuppression?
Genomic Pathway
Non-Genomic Pathway
What Are the Results of Randomized Trials with Steroids? Oral Steroids
Intravenous Steroids
Dose (Single and Cumulative) of Intravenous Steroids and Response Rate
Morbidity and Mortality of Intravenous High-Dose Steroid Pulse Therapy
Peribulbar Injection of Steroids
What Are the Results of Randomized Trials Using Orbital Radiotherapy?
Low Irradiation Dose and Protracted Protocol
Safety of Orbital Radiotherapy
Do You Favour Combined Steroid/Radiotherapy?
What Are the Results of Randomized Trials Using Non-Steroid Immunosuppressants? Cyclosporine
Intravenous Immunoglobulin
Azathioprine and Ciamexone
Tumour Necrosis Factor Blocker
What Are the Results of Randomized Trials Using Somatostatin Analogues?
How Should a Diabetic or Hypertensive Patient with Moderately Severe Graves’ Orbitopathy Be Treated?
What Should You Do if Steroids Fail?
What Is the Optimal Thyroid Treatment in Patients with Graves’ Hyperthyroidism and Moderately Severe Active Graves’ Orbitopathy?
What Are the Actual Evidence-Based Therapeutic Recommendations for Patients with Moderately Severe Graves’ Orbitopathy?
What Were the Recommendations of the EUGOGO Consensus Statement for the Management of Moderately Severe Graves’ Orbitopathy?
What Do the ETA/EUGOGO Guidelines for the Management of Graves’ Orbitopathy Recommend?
Acknowledgements
References
Novel Immunomodulatory Treatment Modalities
Why Look for New Immunomodulatory Treatments?
What Are the Targets for Potential Novel Therapies?
Rituximab. What Is the Rationale for Rituximab?
Does It Work?
What Dose of Rituximab to Give?
Is Rituximab Safe?
Which Patients to Treat?
What Is the Evidence for Other Immunomodulators?
What Are the Most Likely Targets for Therapeutic Intervention? In vitro Studies
Human Studies
Should Clinicians Be Cautious about Trying Novel Immunomodulators?
References
Management of Very Severe Graves’ Orbitopathy: Dysthyroid Optic Neuropathy and Corneal Breakdown
How Do You Define Dysthyroid Optic Neuropathy? What Is the Causative Mechanism?
Are There Specific Risk Factors for Dysthyroid Optic Neuropathy?
Which Symptoms Should Alert Me for Dysthyroid Optic Neuropathy?
What Are the Ophthalmological Signs of Dysthyroid Optic Neuropathy?
Are Additional Investigations Helpful?
How Fast Can Dysthyroid Optic Neuropathy Progress? Is Urgent Treatment Necessary?
What Is the Evidence Base for the Treatment of Dysthyroid Optic Neuropathy?
Are Predictive Factors for Response to Steroid Treatment in Dysthyroid Optic Neuropathy Patients Well Defined?
What Is the Role of Surgery in Dysthyroid Optic Neuropathy?
How Many Patients Become Blind due to Dysthyroid Optic Neuropathy?
How Can I Recognize Corneal Breakdown?
What Is the Recommended Treatment of Corneal Breakdown?
References
Local Treatment Modalities
Is Graves’ Orbitopathy Related to Ocular Surface Pathology?
When and How Should We Support the Ocular Surface?
Can Local Measures Address Eyelid Retraction? Adrenergic Blocking Agents
Anti-Inflammatory Treatment
Botulinum Toxin
Can Local Measures Reduce Orbital Inflammation in Graves’ Orbitopathy?
Can Local Measures Improve the Visual Disturbance and Diplopia?
References
Rehabilitative Surgery
Why Is This Chapter Called Rehabilitative Surgery and Not Cosmetic Surgery?
What Are the Steps and Timing of Rehabilitative Surgery?
How Should Patients Be Selected for Rehabilitative Surgery?
References
Orbital Decompression
What Is Orbital Decompression?
What Are the Aims of Orbital Decompression?
Functional Aims
Rehabilitative Symptomatic Aims
What Are the Different Types of Orbital Decompression?
What Are the Possible Complications of Orbital Decompression?
Can Complications Be Predicted or Prevented?
Are Technical Developments in Decompression Surgery and Other Surgical Rehabilitative Procedures for Graves’ Orbitopathy to Be Expected?
Are Conceptual Developments in Decompression Surgery and Other Surgical Rehabilitative Procedures for Graves’ Orbitopathy to Be Expected?
References
Eye Muscle Surgery
What Are the Reasons for Impairment of Ocular Motility in Graves’ Orbitopathy?
Which Muscles Are Involved?
How Does Decompression Influence Ocular Motility?
How Do You Identify the Affected Muscles?
How Can You Avoid Diagnostic Errors in Complex Cases?
What Is the Optimal Pretreatment before You Start Eye Muscle Surgery?
When Is the Right Time for Surgery?
How Do You Deal with Diplopia until Surgery Is Possible?
How Can You Evaluate the Need for Surgery?
The Surgical Plan: What Procedures Are Recommended?
What Are the Possible Complications of Surgery and How Can I Avoid or Manage Them?
What Can You Realistically Expect from Surgery?
How Can Success of Surgery Be Measured?
How Should You Advise the Patient?
References
Eyelid Surgery
What Are the Indications for Eyelid Surgery in Patients with Graves’ Orbitopathy?
Is Botulinum Toxin Useful?
Is Surgical Intervention Indicated in Corneal Ulceration Secondary to Exposure Keratopathy?
Does Orbital Decompression Have Any Effect on Lid Retraction?
Does Squint Surgery Influence the Lid Configuration?
Can Decompression Be Combined with Lid Lengthening?
What Surgical Procedures Are Available for Correction of Upper Lid Retraction?
Are There Complications?
What Surgical Procedures Are Available for Correction of Lower Lid Retraction?
Should This Be Combined with Horizontal Lid Tightening?
Which Materials Are Suitable for Use as Spacers? Should the Use of Allogeneic Grafts Be Avoided?
Are There Complications?
What about Upper Lid Debulking and Upper and Lower Lid Blepharoplasty?
Does Lid Surgery Improve the Quality of Life of the Patients?
How Can the Effect of Lid Surgery Be Quantified?
References
Quality of Life
What Is Quality of Life?
What Is the Usefulness of Quality of Life Measurements?
What Is Known about General Health-Related Quality of Life in Graves’ Orbitopathy?
Is There a Graves’ Orbitopathy-Specific Quality of Life Questionnaire?
What Are the Results of the GO-QoL?
Can You Explain Response Shift in Quality of Life?
Can GO-QoL Be Used as a Separate Outcome Measurement in Graves’ Orbitopathy?
What Is the Experience with GO-QoL as Outcome Measurement in the Literature?
Are There Other Disease-Specific Quality of Life Questionnaires for Graves’ Orbitopathy?
Are There Qualitative Studies on Quality of Life in Graves’ Orbitopathy?
Is Quality of Life Fully Restored after Treatment of Graves’ Orbitopathy?
What Can I Conclude and Should I Apply the GO-QoL in My Own Practice?
References
Socioeconomic Impact
Is There an Actual Cost Estimation of Thyroid Disorders in Germany and/or Europe?
Does Graves’ Orbitopathy Lead to Occupational Disability?
How Were Data Obtained on Occupational Disability and Impaired Earning Capacity in Graves’ Orbitopathy?
What Are the Findings of the Performed Prospective Study?
How Should We Interpret the Data Obtained on Occupational Disability and Impaired Earning Capacity in Patients with Graves’ Orbitopathy?
What Are the Relevant Implications for the Daily Clinical Practice?
Do We Have Data on the Public Health Relevance of Graves’ Orbitopathy?
References
The Patient’s View
Due to the Changes of My Eyes and Skin I Have Not Only “Lost My Face”! Where Can I Get Support and Help?
Will the Treatment for the Thyroid Make the Eyes Better or Worse?
Can Graves’ Orbitopathy Be Prevented?
Will My Eyes Always Get Worse?
What Can Be Done about Common Eye Symptoms of Graves’ Orbitopathy? Irritation and Redness of the Eyes
Puffiness around the Eyes
Eyelid Retraction
Double Vision
Deteriorating Vision
Will the Eyes Go Back to Normal?
The Changes in My Face Have Affected Me Badly. Can Anything Be Done about Them? Shall I Have My Face Back at the End of Treatment?
Are There Any Risk Factors for a Progressive and Severe Graves’ Orbitopathy?
Can I Contact Patient Support Groups or Fellow Patients?
If Graves’ Orbitopathy Is an Autoimmune Disease, Does That Mean My Immune System Is Collapsed?
After Orbital Radiation, When Will It Be Possible to Have a Baby?
Atypical Manifestations
What Are the Atypical Manifestations of Graves’ Orbitopathy?
What Are Other Diseases Mimicking Unilateral or Atypical Graves’ Orbitopathy?
Are the Clinical Presentation and Management of Unilateral Different from Bilateral Graves’ Orbitopathy?
What Is the Prevalence of Unilateral Graves’ Orbitopathy?
Can We Predict the Course of Unilateral Graves’ Orbitopathy?
What Is Euthyroid/Hypothyroid Graves’ Orbitopathy?
How Will You Manage Euthyroid/Hypothyroid Graves’ Orbitopathy?
What Is Globe Subluxation?
Can Graves’ Orbitopathy Patients without Muscle Swelling Be at Risk for Loss of Vision due to Optic Neuropathy?
References
Childhood Graves’ Orbitopathy
How Frequent Is Graves’ Orbitopathy in Children?
Are Signs and Symptoms of Graves’ Orbitopathy in Childhood Similar to Those in Adulthood?
Why Is Graves’ Orbitopathy in Children and Adolescents Milder than in Adults?
What Medical Treatment for Graves’ Orbitopathy in Children and Adolescents?
What Modality of Treatment for Hyperthyroidism in Children/Adolescents with Graves’ Orbitopathy?
What about Orbital Decompression in Childhood?
References
Comorbidity in Graves’ Orbitopathy
What Is the Risk of Diabetes Mellitus in Graves’ Orbitopathy? Epidemiology
Diagnosis
Management
What Is the Risk of Osteoporosis in Graves’ Orbitopathy? Epidemiology
Management
What Is the Risk of Mental Disorders in Graves’ Orbitopathy? Epidemiology
Management
What Is the Risk of Dry Eye Syndrome in Graves’ Orbitopathy? Background and Epidemiology
Diagnosis
Management
What Is the Risk of Glaucoma in Graves’ Orbitopathy? Background
Diagnosis
Epidemiology
Management
What Is the Risk of Cataract in Graves’ Orbitopathy? Epidemiology
Management
What Is the Risk of Retinopathy in Graves’ Orbitopathy? Background
Management
References
Prevention
What Is Primary, Secondary, and Tertiary Prevention?
What Variables Can Be Modified in the Prevention of Graves’ Orbitopathy?
What Can Be Done in Primary and Secondary Prevention of Graves’ Orbitopathy?
What Can Be Done in Tertiary Prevention of Graves’ Orbitopathy?
What Should One Do when Talking to a Graves’ Orbitopathy Patient Who Smokes?
References
Protocols of Non-Surgical Therapies
What Is the Protocol for Selenium?
What Is the Protocol for Intravenous Glucocorticoids?
What Is the Protocol for Oral Glucocorticoids?
What Is the Protocol for Orbital Radiotherapy?
What Is the Protocol for Cyclosporine?
What Is the Protocol for Rituximab?
References
The Amsterdam Declaration on Graves’ Orbitopathy
What Is the Amsterdam Declaration?
Why Was It Proposed?
Have the Targets Been Met?
Appendix 1: The Amsterdam Declaration
Appendix 2: Signatories of the Amsterdam Declaration
References
Historical Notes on Graves’ Disease
Why Bother about History?
What Is the Earliest Recorded Case of Graves’ Disease and Graves’ Orbitopathy?
What Were the Early Theories about Graves’ Disease and Graves’ Orbitopathy?
Who Were the Most Important Contributors in Developing Our Understanding and Treatment of Graves’ Orbitopathy?
What Lessons Should Be Learnt from the History of Graves’ Disease and Graves’ Orbitopathy?
References
Author Index
Subject Index
