Items in BOLD Discussed in Detail at the Bottom of Outline

Autoimmune Disease and the Eye

Items in BOLD discussed in detail at the bottom of outline

I.Introduction

A.Important for Optometrist to recognize what ocular complications can manifest from autoimmune disease for appropriate treatment, testing, and referral.

II.Goals

A.Recognize signs/symptoms of autoimmune disease affecting the eye

B.Understand systemic complications of autoimmune disease

C.Learn how/when to refer to specialist

III.This lecture is designed to examine the eye (anterior to posterior) and learn how autoimmune disease affects each structure. This is similar to how an Optometrist would discover autoimmune related disease in the eye.

IV.External

A.Ptosis

1.Myasthenia Gravis

a)Chronic autoimmune neuromuscular disease causing muscle weakness

b)Antibodies destroy or alter receptors for acetylcholine. This prevents muscle contraction from occurring.

c)Some patients develop thymoma - need to check thymus gland

d)Eyelid muscles first affected in most cases

e)Test

(1)Tensilon

(2)Ice-pack test

(3)Acetylcholine receptor antibodies

(4)Anti-MuSK antibody

f)Treat

(1)Neostigmine

(2)Pyridostigmine

B.Exophthalmos

1.Graves’ Disease

C.Diplopia

1.Graves’Disease

2.Myasthenia Gravis

3.Multiple Sclerosis

a)Inflammatory (? infectious) disease that causes nerve demylenation

b)Can cause many problems including optic neuropathy and diplopia

c)Typically recover from diplopia without treatment

d)If diplopia appears atypical or combined with other symptoms (numbness, tingling, heat intolerance) - may consider MS testing

4.Giant Cell Arteritis

V.Episclera

A.Not as likely as Scleritis to have systemic association

1.If nodular and/or recurrent, consider list given with Scleritis

VI.Sclera

A.Scleritis

1.Rheumatoid Arthritis

a)Inflammatory damage to small joints in hands and feet

b)Leads to pain, swelling and possible deformity

c)Can cause pain in larger joins such as hip, shoulder, knees, ankles, and elbows

d)Often diagnosed with a combination of blood work, x-ray, and clinical signs/symptoms

e)Treated with NSAIDs for mild cases

f)Can use steroids, DMARDs, and/or immune modulating drugs

g)Most likely systemic cause of scleritis is RA

(1)Keep in mind that only 50% of patients with scleritis have associated condition

(2)Patients with RA and scleritis have a more widespread and aggressive systemic disease and may need more aggressive therapy

2.Lupus

a)Lupus is an autoimmune disease that can affect: joints, skin, kidneys, blood cells, brain, heart and lungs

b)Signs and symptoms often include: fatigue, shortness of breath, chest pain, classic “butterfly”rash on cheeks and nose

c)Most commonly seen in women of childbearing age

d)Difficult to diagnose

e)Treated with NSAID, steroid, Plaquenil, immune suppression

3.HLA-B27 Disease (not as likely) - see discussion on Uveitis for diagnosis strategy

a)Ulcerative Colitis

b)Ankylosing Spondylitis

c)Reactive Arthritis

d)Psoriatic Arthritis

VII.Cornea/Dry Eye

A.Sjogren’s

1.Autoimmune disease that mainly causes: dry eye and dry mouth

2.Can also have joint pain, fatigue, persistent cough

3.Typically in women over 40

4.Can have association with RA or Lupus

5.Diagnosis is made by signs/symptoms, blood test, lip biopsy?

6.Treat specific symptoms

7.Treat salivation (pilocarpine), may also use Plaquenil

B.Graves’Disease

C.Lupus

D.Rheumatoid Arthritis

VIII.Uvea/Uveitis

A.Ulcerative Colitis

B.Ankylosing Spondylitis

C.Reactive Arthritis

D.Psoriatic Arthritis

E.Rarely Lupus

F.Sarcoidosis

IX.Retina

A.Vasculitis

1.How to recognize vasculitis

2.Who to refer to

B.Plaquenil Retinopathy

C.Arterial Disease

1.Giant Cell Arteritis

X.Optic Nerve

A.Multiple Sclerosis

B.Sarcoidosis

C.Lupus

D.Giant Cell Arteritis

1. Graves’ Disease

I.Graves Disease (GD) is an autoimmune disease that targets 3 tissues

i.Orbit

ii.Thyroid

iii.Skin

a.Previous thinking was that GD damaged the thyroid gland which led to ophthalmic complications

b.Current knowledge states that GD is an autoimmune disease that can affect orbit, thyroid, and skin independently. It is not the thyroid directly leading to ocular damage.

II.Pathogenesis

a.Body produces autoantibodies to TSH receptor which chronically stimulates synthesis.

i. Leads to abnormally high T3 and T4

ii.Negative feedback loop decreases TSH which increases T3 and T4

b.Simultaneously affects orbit fat and muscle

i.Fibroblasts

ii.Myofibroblasts

III.Ocular Signs and Symptoms

a.Exophthalmos –always bilateral though often asymmetric

i.Most common cause at 50%

b.Dry eye

i.Foreign body sensation, Epiphora

ii.If severe enough can lead to corneal complications

c.Eye Pain

d.Diplopia–possible muscle restriction

e.Eyelid retraction - from overactive sympathetic innervations to upper eyelid

f.Redness

g.Rarely Optic Nerve Compression

IV.Thyroid Labs

a.Hyperthyroidism

i.Majority of patients with GD get this ~80%

ii.Nervousness

iii.Heat Intolerance/Sweating

iv.Tremor

v.Increased appetite

b.Hypothyroidism

i.Uncommon in GD –but up to 15%

ii.Lethargic

iii.Low appetite

iv.Low sex drive

v.Weight gain

vi.Cold, clammy

c.Euthyroid

i.Uncommon in GD ~ 5%

ii.No thyroid symptoms

iii.Skin Manifestations

iv.Pre-tibial

V.Treatment

a.Most patients stabilize over 8-36 months

b.Systemic Steroids

c.Radiotherapy

d.Anti-thyroid medication

e.Thyroidectomy

f.Psychiatric Medication

i.Quality of Life

g.Orbital Decompression

i.Likely need strabismus surgery also due to diplopia

1.As high as 64% after decompression

h.Topical Lubrication

i.Treating exposure keratopathy

i.Smoking cessation!

i.Helps progression of disease

ii.Helps prognosis for recovery

iii.Non-smokers (or those who quit) do better with treatment

iv.Weight loss

j.Neuropsychological and Mental Health

i.Often overlooked symptom of Graves’

ii.Depression

iii.Tension

iv.Anxiety

2. Giant Cell Arteritis

a.Giant Cell Arteritis (GCA) is an Immune-Mediated Vasculitis

b.Affects Medium and Large Arteries

i.In eye mostly Posterior Ciliary Artery (PCA), then Central Retinal Artery (CRA), rarely Ophthalmic Artery (OA)

ii.Explain why GCA affects eyes

iii.Called GCA because of granulomatous inflammation. Arteries lined with multinucleated giant cells: macrophages, lymphocytes, and fibroblasts

c.Incidence of 2.3/100,000 in 6th decade. Increases with Age.

d.Happens mostly to those > 50 years old

i.Age range

e.Predilection for North European, Scandinavian descent. Typically Caucasian though can happen in other races

f.Why is it important?

i.Profound vision loss

1.Causes A-AION

2.Can become bilateral in 14 days in 1/3 if untreated

3.Treatable

g.CRAO and Cilioretinal artery occlusion can occur

h.A-AION

i.Sudden painless vision loss

ii.Unilateral Optic Disc Edema

iii.1/10 patients (> 50 years old) with optic disc edema are A-AION. Other 9/10 NA-AION

i.Systemic Symptoms

i.Jaw Claudication (Odds Ratio 9.0)

ii.Neck Pain (Odds Ratio 3.4)

iii.Anorexia

iv.Less predictable symptoms

1.Headache

2.Fever

3.Scalp Tenderness

4.Malaise

v.Average number of symptoms =

j.Visual Symptoms/Signs

i.Sudden, painless vision loss

ii.31% had amaurosisfugax 1-2 weeks before

1.This can be misleading. Not saying 31% of patients with AmaurosisFugax have GCA

iii.6% diplopia

iv.8% ocular pain

v.Optic Disc Edema “chalky white pallor”

k.Lab Testing

i.ESR –86% sensitive

ii.CRP –100% sensitive, 82% specific

iii.Combined ESR and CRP –99% sensitive, 97% specific

iv.CBC with differential looking for disease that can affect Red Blood Cells (i.e. Anemia, Polycythemia Vera)

l.Other Diagnostic Testing

i.Fluorescein Angiography (FA) –characteristic late filling of choroid in the 2 weeks after Optic Disc Edema starts

ii.Ultrasound, PET, MRI of limited benefit

iii.Temporal Artery Biopsy –especially indicated if clinical symptoms highly suggestive but either ESR or CRP are inconclusive

m.Contralateral optic nerve can give us clues to A-AION vs. NA-AION

i.Go through Bayesian analysis

1.If C/D is > 0.4 1/5 have A-AION

2.If C/D is < 0.3 1/15 have A-AION

n.Treatment

i.Most studied and likely still most effective is oral steroid

1.80-100 mg/day until labs normalize

2.Then taper for VERY long (years!)

3.Evidence still lacks because not ethical to have a placebo group

ii.No evidence that IV steroid in mega dose any more effective

iii.Limited evidence for TNF blockers, Methotrexate and other immune modulators

3. Uveitis

II.The Goal of Treatment

A.Improve patient’s quality of life

III.Associated Conditions

A.What is the purpose of evaluating for associated conditions?

1.Find something that once found will help alleviate uveitis and prevent recurrence.

2.Correctly name a condition that was previously named incorrectly –leading to better treatment of non-ophthalmic condition

3.Should leave the patient better after the testing

B.We need a thoughtful approach that matches the description of uveitis with patient’s symptoms.

C.A “scatter”approach is not good medical care because:

1.It is no more beneficial to patient than tailored approach

2.There is added expense

3.There is added anxiety

4.Increase in false positives

V.A tailored workup should be specific to your patient. It requires that you know:

A.A working list of common associated conditions

B.The characteristics of the uveitis of those conditions

1.Acute vs. Chronic –Can be acute and recur. Recurrent does not mean Chronic

2.Anterior vs. Posterior (or Panuveitis)

3.Unilateral vs. Bilateral (or Alternating)

4.Granulomatous vs. Non-Granulomatous–Often difficult to distinguish. Look for Granulomas, Bussaca nodules or Mutton Fat KP

C.The history and physical findings that might manifest in a patient with one of these conditions

D.What specialized testing used to identify these conditions (if indicated)

E.The appropriate referral/treatment when a condition is diagnosed or suspected

F.Meshing these five areas will allow for appropriate testing and eliminate unnecessary tests. (e.g. a patient with acute, unilateral, non-granulomatous uveitis should not be tested for Sarcoid.)

VI.Common associated conditions and their characteristics

A.Ankylosing Spondylitis, Reactive Arthritis, Psoriasis - Acute, anterior, unilateral, nongranulomatous.

B.Inflammatory Bowel Diseases–Typically unilateral and non-granulomatous. However, some report up to 50% bilateral. Forty percent of uveitis is anterior (40% is panuveitis, 20% posterior)

C. Juvenile Idiopathic Arthritis–Chronic, anterior, unilateral or bilateral, nongranulomatous, asymptomatic. “White eye uveitis.”

D.Sarcoid –Chronic, anterior (can be posterior or pan), bilateral, granulomatous

VII.Signs/Symptoms, Follow-up Testing, and Treatment of Associated Conditions

A.Ankylosing Spondylitis

1.Lower back pain/stiffness in morning > 30 minutes, back pain improves with exercise, awakening in second half of night from back pain. All back pain is worse with rest.

2.Sacro-iliac joint x-ray and referral

3.Treatment typically NSAID. TNF Blockers work very well but are very expensive

B.Reactive Arthritis

1.Most patients with Reactive Arthritis lack the full triad of “Reiter’s Syndrome.”Acute, asymmetric oligoarthritis (typically knee, ankle, foot). Can also have symptoms of urethritis, diarrhea, or cutaneous lesions (usually soles of hands or palms of hands). Musculoskeletal symptoms follow GI or GU symptoms by 2-4 weeks.

2.Refer to Rheumatology. Laboratory tests are not indicated for diagnosis.

3.Treatment is pain management. This includes, but not limited to, Physical Therapy, NSAID, Steroid, Anti-rheumatic medication.

C.Inflammatory Bowel Disease

1.GI symptoms such as stomach cramps, diarrhea, bloody stools

2.Refer to GI

3.Treatment has a multi-step approach: Fiber, Aminosalicylates, and Corticosteroids

D.Psoriasis

1. Plaques on skin - red with white scaly top

2.Can affect scalp, skin near joints

3.Refer to dermatology

4.Treatment includes shampoos, ointments, immune modulation

E.Juvenile Idiopathic Arthritis

1.Suspect in children with non-traumatic iritis. Usually found with unilateral cataract and white eye uveitis.

2.Possible joint pain/stiffness

3.Refer to pediatrician

4.Treatment typically NSAID.

F.Sarcoid

1.Skin involvement (Macules, Papules, Granulomas), pulmonary symptoms such as dyspnea or cough

2.Order chest x-ray. Refer. ACE is a non-specific test with a poor sensitivity.

3.Treatment: Immune suppression. Typically Corticosteroids.

4. Plaquenil Retinopathy

VI.Hydroxychloroquine (Plaquenil)

a.Used for

i.Lupus

ii.Rheumatoid Arthritis

iii.Sjogren’s

iv.Lyme arthritis

b.Several side effects. Mostly worried about vision changes

c.Damages Ganglion cells, Photoreceptors, RPE

i.Leads to atrophy of macular tissue 5-10 degrees from fovea

ii.Paracentral scotoma

iii.Irreversible damage

d.Risk Factors

i.Age > 60*

ii.Retinal Disease? –possibly

iii.Renal and/or Liver Disease

iv.Daily Dose

v.Cumulative Dosage

e.Daily Dose

i.Typically 400 mg/day

ii.Used to worry about weight

iii.Does not store in fatty tissue

iv.Concern now with height/ideal weight

f.Cumulative Dosage

i.1000 g = 400 mg/day for >5-7 years

ii.If patient takes for less than 5 years, risk is 1/1000

iii.If patient takes for greater than 5 years risk is 1/100

VII.Testing

a.Should not be confused with “screening”

b.Several tests are widely used

i.Amsler Grid

ii.Color vision

iii.10-2 Visual Field

iv.Multifocal ERG (MFERG)

v.Fundus Autofluoresence (FAF)

vi.OCT

vii.Fundus examination

c.The following tests are not recommended

i.Time domain OCT

ii.Fluorescein Angiography

iii.Full Field ERG

iv.EOG

v.Amsler Grid/Color Vision –not sensitive enough

d.MFERG

i.Pros

1.Objective

2.Reliable

3.Targets macula

ii.Cons

1.Interpretation

2.Expense

3.Hassle

4.Accessibility

e.FAF

i.Pros

1.Objective

2.View changes over time

ii.Cons

1.Interpretation

2.Availability

3.Not as reliable as 10-2, SD-OCT, ERG

f.10-2 Visual Field

i.Pros

1.Available

2.Inexpensive

3.Easy interpretation

ii.Cons

1.Subjective

2.Patients dislike

3.False positives!!

g.SD-OCT –Look for Flying Saucer sign

i.Pros

1.Available

2.Objective

3.Interpretation easy

4.Good Specificity

ii.Cons

1.Early detection may be difficult

2.Poor sensitivity

3.Cost

VIII.American Academy of Ophthalmology 2002 recommendations

a.Patient is high risk if > 6.5 mg/kg/day

b.Color vision

c.10-2 or Amsler Grid

IX.American Academy of Ophthalmology 2011 recommendations

a.High risk if 1000g cumulative dose

b.Consider height

c.No color vision or Amsler Grid testing

d.Should do 10-2 combined with

i.SD-OCT, FAF, mfERG

e.Recommend baseline exam

i.If high risk, test yearly

ii.If low risk, test again after 5 years

II.American Academy of Ophthalmology 2011 recommendations

a.High risk if 1000g cumulative dose

b.Consider height

i.5'5" for men

ii.5'7" for women

iii.For every 2" below ideal, subtract 1 tablet per week

c.Consider weight

i.180 lbs for 400mg

ii.Subtract 1 tablet per week for every 13 lbs less

d.No color vision or Amsler Grid testing

e.Should do 10-2 combined with

i.SD-OCT, FAF, mfERG

e.Recommend baseline exam

i.If high risk, test yearly

ii.If low risk, test again after 5 years

X.Frustrations with diagnosing and managing Plaquenil Maculopathy

a.False positives

b.There is no gold standard

c.We are the authority –often the eye doctor will dictate who gets taken off meds

d.Difficult to balance risks/benefits of Plaquenil

e.It is possible that we are taking many patients off Plaquenil that would greatly benefit from the medication. These patients may have discontinued it due to our recommendations. We may have arrived at the recommendation from false positive testing. Optometrists need to understand our role in this diagnosis and management and be very careful before recommending stopping a potentially very helpful medicine.