GRAVES’ ORBITOPATHY GRAVES’ ORBITOPATHY LARRY H ALLEN IVEY EYE INSTITUTE-UWO LONDON ONTARIO

GRAVES’ ORBITOPATHYGRAVES’ ORBITOPATHY

LARRY H ALLENIVEY EYE INSTITUTE-UWO

LONDON ONTARIO

GRAVES’ ORBITOPATHYGRAVES’ ORBITOPATHY

GRAVES’ ORBITOPATHY

WORLDWIDE INCIDENCE

SMOKING

RI 131

THERAPY

GRAVES’ OrbitopathyGRAVES’ Orbitopathy

Assumed to be Autoimmune.Fibroblast most likely target cell with sub-

populations 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 Ophthalmopathy andThyroid statusstatus

40% Concurrent Hyperthyroid20% Ophthalmopathy Before Hyperthyroid20%Ophthalmopathy After Hyperthyroid15-20% Ophthalmopathy Within 6 Months

of each other Before or After DiagnosisUsually Clinical Signs Preceed CT/MR/US

Findings

InvestigationsInvestigations

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’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 CIGSGRAVES’ 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’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 IGRAVES’ 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’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 THERAPYGRAVE’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 ?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%)


Are there risk factors for progression of the Orbitopathy after R I therapy

YES,Smoking,Hyperthyroid severity, Late correction of post-R I Hypothyroid state, and highTRAb levels


Can progression of Graves’ Orbitopathy be prevented

YES. With oral Steroid Prophylaxis


Are Steroid Dose, Timing of the initiation of therapy after R I, and Duration of therapy well defined

NO


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’ THERAPYGRAVES’ THERAPY

Severe disease or O N compression IV steroid better than oral but more side-

effects.Steroid often work better with other anti-inflammatory 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’ RTXGRAVES’ 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 RTXLHA soft tis. 60% have had good results

with RTX/steroid and ON disease.

GRAVES ‘ TherapyGRAVES ‘ 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 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’GRAVES’

GRAVES’GRAVES’

GRAVES’ DISEASEGRAVES’ DISEASE

THE PUZZLE CONTINUES

ACNE ROSACEAACNE ROSACEA

OCULAR ROSACEA

ACNE ROSACEAACNE 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 ROSACEAOCULAR 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.


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.


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 THERAPYA 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 RA R2 WEEK INTERVAL

FLOPPY EYELID SYNDROMEFLOPPY EYELID SYNDROME

FLOPPY LIDFLOPPY LID

Flaccid lid tissue. Ant. surface symptoms.Tarsus Velvet papillary appearance.Lash ptosis often seen before lid gets floppyLid 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 LIDSFLOPPY LIDS

Sleep Apnea ass. with BP,Arrhythmia.3x increase in MVATx. 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.



LASH PTOSIS

UPDATEUPDATE

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.

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GRAVES’ ORBITOPATHY GRAVES’ ORBITOPATHY LARRY H ALLEN IVEY EYE INSTITUTE-UWO LONDON ONTARIO