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GRAVES’ ORBITOPATHY
LARRY H ALLEN
IVEY EYE INSTITUTE-UWO
LONDON ONTARIO
GRAVES’ ORBITOPATHY
GRAVES’ ORBITOPATHY
WORLDWIDE INCIDENCE
SMOKING
RI 131
THERAPY
GRAVES’ Orbitopathy

Assumed to be Autoimmune.
 Fibroblast most likely target cell with subpopulations to include adipose cells, GAGS
production and Cytokine release.
 Target sites appear to in the reto-orbital
tissue most likely the EOM.
 Unclear association with the thyroid .
Ophthalmopathy andThyroid
status

40% Concurrent Hyperthyroid
 20% Ophthalmopathy Before Hyperthyroid
 20%Ophthalmopathy After Hyperthyroid
 15-20% Ophthalmopathy Within 6 Months
of each other Before or After Diagnosis
 Usually Clinical Signs Preceed CT/MR/US
Findings
Investigations

TSH, Free T4, Thyroid Antibodies.
 No association between Thyroid antibodies
and disease severity nor progression.
 Pre- tibial Dermopathy is often associated
with more severe disease.
 10% of Graves’ patients are Euthyroid.75%
may convert to abnormal Thyroid < 2 yrs.
GRAVES’

Worldwide decrease in incidence EXCEPT
in Eastern European countries where there
is an increase of 30% and an increase in
SMOKING of about 30%!
 European survey showed same or decreased
incidence in 85% of respondents.12% of
respondents indicated an increase and were
from those in E. Euorpean areas.
GRAVES’ AND CIGS

Cleaners in Amsterdam Thyroid clinic complained
why this clinic had so many cigs to clean up. 1st
association!!
 60% Grave’s smokers: 20% gen . Population:
MAYO study 40% smokers.
 Cig smoking ass. with delayed response to steroid
and RTX therapy.Therapy longer in cig smokers
and lack of response to therapy higher.
GRAVES’

Steroid Tx. for optic neuropathy in 1 study
showed results to be better in non smokers.
 94% vs 68% better for non smoker grp.
 Cig smokers also have a higher Recur and
Relapse rate of Hyperthyroid state.
 Cig smoking one of the major risk factor s
and is MODIFIABLE !!!
GRAVES’ R I

R I Tx. May aggravate the orbitopathy.
 Ablation of the thyroid liberates Ab that
may increase the immune response in the
orbit.
 Studies show an increase in blood levels of
TSHR Ab after R I
 Higher levels in smokers!
GRAVES’

One study show R I alone vs Oral vs Sx.
That aggravation seen in 35%;16%;12%.
 Bartalena showed R I alone vs R I + oral
steroid saw progression of 15% vs 0%.
 However many feel that early ablative Tx
better overall.? Is this a factor in the
reduction in incidence in some countries?
GRAVE’S R I THERAPY

Suggested Tx Timetable In General.
 Oral Tx to stabilze thyroid for 6/12.
 Mild inflammation R I alone.
 Moderate to severe R I+steroid for 6-8wk.
 Treat hypothyroid state early.
 Reduce or stop smoking.
 Some centers treat all with steroid+R I.
Orbitopathy and R I ?

Does R I therapy
cause a progression in
of Graves”
Orbitopathy

YES, in a definite
proportion of patients
(about 15-20%)
Orbitopathy and R I ?

Are there risk factors
for progression of the
Orbitopathy after R I
therapy

YES,Smoking,Hypert
hyroid severity, Late
correction of post-R I
Hypothyroid state, and
highTRAb levels
Orbitopathy and R I ?

Can progression of
Graves’ Orbitopathy
be prevented

YES. With oral
Steroid Prophylaxis
Orbitopathy and R I ?

Are Steroid Dose,
Timing of the
initiation of therapy
after R I, and Duration
of therapy well
defined

NO
Orbitopathy and R I ?

Should All patients
given R I therapy be
given Steroid
Prophylaxis

Steroid Prophylaxis
may be avoided in
patients with absent or
inactive Orbitopathy
provided other risk
factors are Absent ie
Smoking , Orbital
inflammation etc.
GRAVES’ THERAPY

Severe disease or O N compression
 IV steroid better than oral but more sideeffects.Steroid often work better with other antiinflammatory agents ex. Cyclosporin but again
S.E. to be considered.Cambridge Protocol
reduction in Sx intervention (EYE 2006)
 Variable results with local steroids and other meds
eg., somatostatin analogs,Immunosupressants.
 Biologics ie Rituximab and others
GRAVES’ RTX

Radition of orbit and retro-orbital tissue
controversial.
 Mayo study no benefit:1 Dutch study
inconclusive:Italian grp feel helpful in 60%
soft tissue changes.
 No study ON compreesion and RTX
 LHA soft tis. 60% have had good results
with RTX/steroid and ON disease.
GRAVES ‘ Therapy

Surgical Orbital Decompression to enlarge
the Orbit and allow for expansion of the
enlarged EOM bellies into the Sinus area
and thus reduce the Optic Nerve
Compression and Orbital Congestion.
 Not without its problems ie variable amts of
decompression,Diplopia , reduction in
Proptosis
GRAVES THERAPY
Should Anti –Smoking therapy and
Campaigns be more aggresively applied to
patients with Graves’ Disease.
 Case reports of Graves’ disease improving
after cessation of SMOKING only.

GRAVES’
GRAVES’
GRAVES’
GRAVES’
GRAVES’ DISEASE

THE PUZZLE CONTINUES
ACNE ROSACEA

OCULAR ROSACEA
ACNE ROSACEA

Chronic skin disorder. Middle age(30-60).
 Idiopathic in origin affecting fair skin,fair
hair individuals 1*.
 Ocular Rosacea inflammatory in the clinical
setting.
 Ass. with increased levels of IL-1a and
MMP. Bacterial lipases also a factor.
OCULAR ROSACEA
Tetracyclines inhibit MMP’s and lid
bacterial lipase production thus reducing
free fatty acids in tear film.
 Tetracyclines will improne tear BUT.
 Most studies with tetra. involve cutaneous
AR .Ocular R Tx an assumed extension.
 Tetra. Reduce bacterial flora of eyelids.

OCULAR ROSACEA

Tetra. 2*reduce lipases and FFA which are
toxic to cornea and also improve the tear
BUT.
 Reduce neutrophil chemotactic factors and
lid inflammation .
 Rosacea associated with an increased
prevalence in chalazions,recurrance,and
multiplicity.LHA study AR 48% of cases.
OCULAR ROSACEA

Thought to be under recognized by Ophthal.
 Tx is prolonged.High patient compliance is
needed.Systemic and local Tx required.
 Clinically ocular Rosacea more
inflammatory than infectious-LHA.
 Tx with Tetra’s,Minocycline,Doxycycline
oral.TopicalAb-steroid ung beneficial.
A R THERAPY

Doxy.50-100 mg bid for 2 wks then once
daily 2-3/12 Cycles of 3-6/12, on –off.
 Mino.50-100 mg similar fashion. Mino
more anti-inflamm. More sideffects.
 S.E. GIT,Photosensitive,yeast infx.
 Topical steroid +/- Ab. ,2-3 wks to settle.
 Lid hygiene
A R

2 WEEK INTERVAL
FLOPPY EYELID SYNDROME
FLOPPY LID

Flaccid lid tissue. Ant. surface symptoms.
 Tarsus Velvet papillary appearance.
 Lash ptosis often seen before lid gets floppy
 Lid laxity Upper>lower lid or canthus.
 Middle age,M>F,LARGE,sleep prone.
 Ass. Sleep Apnea in 8%.
 Sleep Apnea ass. 2% Floppy lid.
FLOPPY LIDS

Sleep Apnea ass. with BP,Arrhythmia.
 3x increase in MVA
 Tx. includes shield in PM initially with lid
tightening as Sx difinitive therapy.
 Sleep lab for Dx. and CPAP to reverse
apnea. ? Other TX modalities of value.
 Diet and WT loss beneficial.
FLOPPY LID
FLOPPY LID

LASH PTOSIS
UPDATE

THANK YOU for the opportunity to
participate in this Update In Ophthalmology
and Medicine , to the Planning Committee ,
and to Natalie for her administrative
expertise.