Lecture 4b thryoid related eye disease updated 2019

Bệnh nhãn giáp là biểu hiện ở mắt của các bệnh liên quan tuyến giáp. Bệnh lý này có nhiều tên gọi khác nhau như bệnh Graves, bệnh nhãn giáp, bệnh lý hốc mắt của Graves hay bệnh mắt liên quan tuyến giáp.

Thyroid Eye Disease

Kenn Freedman MD PhD

TTUHSC Department of Ophthalmology and Visual Sciences

Thyroid Related Eye Disease

Many Different Names

Thyroid Related Orbitopathy (TRO)

Thyroid Associated Orbitopathy (TAO)

Thyroid Eye Disease (TED)

Graves Ophthalmopathy (GO)

Thyroid Related Immune Orbitopathy (TRIO)

Normal Eyelids and Orbit

LPS – Levator Palpebrae Superioris

Normal Eyelid Positions

Upper- 1-2 mm below upper limbus

Lower - at lower limbus

LPS

Levator

From Eyeimaginations

Optic Nerve

Some Terminology

and risks

Orbital Disease and Thyroid Status

 TRO diagnosed

before hyperthyroid - 22%

simultaneous hyperthyroid - 20%

following hyperthyroidism - 57%

*Some never hyperthyroid

*May occur with Hashimoto’s thyroiditis and hypothyroidism

TED can be seen at any level of thyroid status

thyroid gland (also called Thyrotropin Receptor Abs)

* use in diagnosis when patient Euthyroid

* can be a measure of active inflammatory phase

Other Antibody Tests

Thyroid Peroxidase

antibody

TPO Ab Hashimoto’s or

Graves Disease (Autoimmune Thyroiditis)

Thyroglobulin

antibody

Tg Ab Hashimoto’s or

Thyroid Cancer

Thyroid Eye Disease

Disease

clinically serious manifestations

Graves Disease and TED

Graves Disease and Ophthalmopathy

 Chronic non-granulomatous

inflammatory process spreading apart muscle fibers

Graves Ophthalmopathy – 2 Phases

Congestive signs –

Lid edema and erythema,

Chemosis and injection of conjunctiva Injection over the muscles

Ptosis

Painful?*

- Patients can be uncomfortable,

significantly painful period

~18 months

(3-36 months)

Proptosis, Eyelid retraction resulting in corneal

exposure problems

Lateral Tarsorrhaphy

Graves Ophthalmopathy – 2 phases

 1 Inflammatory Phase – self limited, ~ 3 – 36 months

Complications can arise during this period

Treatment with Steroids (IV or oral) ? Radiation? - to help prevent complications* Index of Inflammatory Phase – TSI – (OPRS 2006; 22:13-19)

 2 Cicatricial /Fibroblastic Phase

Depositing by fibroblasts of Glycosaminoglycans and Collagen

Results in classic signs of TRO

Lid retraction

Proptosis Lid Lag Restrictive Myopathy

Active Inflammatory and

Chronic fibrotic Phases

20% 60% 20%

% - frequency of pts presenting with TRO

Chronic phase does not return

Normal Eyelids and Orbit

LPS – Levator Palpebrae Superioris

Normal Eyelid Positions

Upper- 1-2 mm below upper limbus

Lower - at lower limbus

LPS

Levator

From Eyeimaginations

Clinical Signs

 Very Specific sign up to 92%

(Lateral Lid Flare Sign)

UL Retraction most common sign

(LPS fibrosis, overactive of LPS or Muller's Muscle?)

DDX: Eyelid Retraction

Graves Ophthalmopathy- #1 – unilateral or bilateral

Other Causes of Hyperthyroidism

Other Orbital Inflammatory or Neoplastic Conditions

– Orbital Pseudotumor, FB, Granulomatous Inflammation, Neoplasm

Cicatricial Process

Skin or Posterior Lamellar

(Trauma, Burns, Systemic or Local Inflammatory Disorders)

Trauma / Post-Operative

Entrapped Inferior Rectus

Vertical Rectus Muscle Recession Surgery

S/P Eyelid or Conjunctival Surgery

Neurologic

- e.g Dorsal midbrain syndrome (Collier’s sign) , aberrant regeneration of the 3 rd CN

Metabolic (thyroid, cirrhosis, uremia, Cushing’s syndrome, hypokalemia)

Pharmacologic – Sympathomimetic, corticosteroids

Congenital – persistent or periodic unilateral retraction reported

Physiologic / Normal Variant – about 2% of population has MRD>5.3mm/ Scleral Show

Pseudo-retraction

– Contralateral Ptosis (Herring’s Law)

- Proptosis

- Lower Lid Laxity

- Large Myopic Eye, prominent glaucoma filtering bleb

Graves : Proptosis, LL retraction

Problems: Exposure keratopathy and globe luxation

Globe Luxation

 Orbital Deformity (e.g Crousson’s syndrome)

Recall: Patient with floppy eyelid syndrome who ended up with bilateral optic neuropathy

Displacement of the globe outside

of eyelids

Patients can present in so many ways Young woman with just

proptosis OS and lid lag on downgaze.

Restrictive Myopathy

EOM involvement:

IR > MR >> SR > LR

 (note specifically in abduction)

What is your first impression?

What do you see?

Left elevation deficit and a Left Hypotropia worse on upgaze

What are the most

common causes of

this?

Thyroid Eye Disease

Orbital Floor Fracture

Multiple Studies done:

MRI Brain and Orbits (shown)MRA of Brain – negative

MRA of Neck

Enlarged muscles not mentioned in report

Diplopia - Double Vision

 Optical Problems

– Quite common- e.g astigmatism, cataract, corneal disease

 Strabismus – misalignment

- Neurological – Cranial Nerve Palsy (CNP), High ICP, Inflammatory (e.g MS)

- Myogenic – Myasthenia Gravis (MG)

- Orbital – EOM restriction

– Trauma, Inflammation (TED) , Tumor

Evaluation:

- Ophthalmic Evaluation

- Neuroimaging – MRI Brain or CT Orbits - When appropriate - e.g non isolated CNP

- Lab: TFTs, MG testing

Urgency – depends on timing of onset and neurologic findings

Most CNPs are microvascular

Most MG presents with ocular symptoms and is not yet life threatening

EOM enlargement

Beware of Iodine Contrast

Graves Disease

 Rarely do I order CT of the orbits with contrast ,

but especially not in patients where suspect TED

IR enlargement OS - MRI

TED: Patterns of Strabismus

 Esotropia

 Hypotropia / Hypertropia

 Exotropia - uncommon

Think about MGAssociation with TED

Esotropia

Right Hypotropia

Other possible signs

 Ptosis

 Thyroid Associated “Periorbitopathy”

Eyebrow fat and soft tissue

expansion Archives 2012;130:319 and 1566

Graves patient with proptosis LL retraction and ptosis

* Surgical Thyroidectomy thought to reduce risk of TED

(JAMA Oph 2015;133:290)

treatment with steroids appears to curtail these exacerbations.

Treatment

Inflammatory/Active Phase of TED

Supportive, Wait it out

“In general we don’t aggressively treat the eye disease during the active phase unless the vision is threatened” - Neil Miller , Eyenet May 2002

- Vs Aggressive Treatment with Corticosteroids or Radiation*

Monitor Vision for signs of Compression

Lubrication, Possible Tarsorrhaphy

Stop Smoking, Reduce sodium intake

Attaining Euthyroid Status

Active Inflammatory and Chronic fibrotic Phases

20% 60% 20%

% - frequency of pts presenting with TRO

Chronic phase does not return

- Radioactive Iodine Treatment/ Ablation

Supportive Treatment (exposure)

Clearly useful though in compressive optic neuropathy

- Selenium, Methotrexate, Rituximab

- Orbital Radiotherapy - complicates further surgical procedures

- Surgical – Orbital decompression, Tarsorrhaphy

Hyperthyroid pt with severe chemosis, proptosis and corneal exposure and ulcers Bilateral lateral tarsorrhaphies were urgently done to protect corneas

Treatment

Role of Steroids, Radiation:

uncertain benefit.

- OPH 2001: 108:1523 – no benefit

- JNO 2007,27:205 Review of Corticosteroids and XRT (Inadequate evidence to ascertain whether CS or XRT shortens the active phase of the disease or improves long term

disfigurement or disability)

Other Treatments

Methotrexate for treatment of Thyroid Eye Disease

Hindawi Publishing Corporation

Journal of Ophthalmology

Volume 2014, Article ID 128903, 5 pages

http://dx.doi.org/10.1155/2014/128903

Rituximab – Monoclonal antibody

 Ophthal Plast Reconstr Surg 2010 Sep-Oct;26(5):310-4 doi:

10.1097/IOP.0b013e3181c4dfde.

 Rituximab for thyroid eye disease.

 Silkiss RZ 1 , Reier A , Coleman M , Lauer SA

Trade name: Rituxan

A monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B-cells Rituximab destroys B cells and is therefore used to treat Lymphoproliferative disorders that involve B cells –

including lymphoma and inflammatory / autoimmune

conditions which include orbital pseudotumor and

Thyroid Ophthalmopathy

TED IOIS Lymphoma

Use of Rituximab

improvement of active Graves Orbitopathy

 Initial Study – 12 patients with TED treated with Rituximab showed clinical improvement

Ophthal Plast Reconstr Surg 2010 Sep-Oct;26(5):310-4 doi: 10.1097/IOP.0b013e3181c4dfde.

Rituximab for thyroid eye disease.

Silkiss RZ 1 , Reier A , Coleman M , Lauer SA

Compressive Optic Neuropathy

 Possible Signs:

 RAPD

VF loss from optic nerve compression

Treatment of

Compressive Optic Neuropathy

1 Systemic High Dose Steroids

If fail, or recurrence on tapering consider

Orbital Decompression

 Indications

Compressive Optic Neuropathy

Severe Proptosis resulting in Exposure problems

Globe LuxationSevere Disfigurement

Summary of Treatment of Active Inflammatory Disease

From JNO 2014; 34:186

Surgical Planning - order

Tarsorrhaphy Orbital decompression Muscle Procedures Lid Retraction Surgery

Can confuse hypotropia with UL retraction orHypotropia can accentuate appearance of UL

retraction

 One reason to do eye

muscle surgery before

eyelid surgery

Muscle (EOM) Procedures

 Wait for stability of measurements and resolution of inflammatory component Want also stability of

Thyroid Hormone status

 GOAL: release of restriction

Esotropia – Unilateral or Bilateral MR Recession(s)

Hypotropia – Unilateral IR recession

 Surgical numbers in tables of limited value

 Adjustable suture - under anesthesia

IR recession 2.5-3 PD/mm

Upper Lid Retraction

1 Levator Recession

a Anterior approach

b Posterior approach *

2 add small Tarsorrhaphy (lateral canthoplasty) for the lateral scleral show

3 Subconjunctival Botulinum Toxin A

(OPH 2002; 109:1183, and OPRS 2004; 20:181-185)

Botulinum Toxin for UL Retraction

temporizing measure for UL retraction until stability for surgery is reached.

just above superior tarsal border in the

elevator complex

Levator Recession

Lower Lid Retraction

Lower Lid Retractor Lengthening Procedure

Uses scleral or cartilage or artificial spacer

e.g eyeplastics.com/eyelid –lid-retraction-thyroid-eye-disease

 TED effects Orbital Tissues – with implications for

optic nerve, extraocular muscles and Eyelids

 Corticosteroid treatment – is useful at times in these patients, especially if they have compressive optic neuropathy

O LORD, our Lord, how

majestic is your name in all the earth!

Psalm 8:1

Banff NP , Alberta Canada