BRITISH OPHTHALMOLOGICAL SURVEILLANCE UNIT
CONDITION TO BE STUDIED
Dysthyroid Optic Neuropathy (DON)
-----------------------------------------------------------------------------------------------------------------INVESTIGATORS
Yun Wong -Principal investigator
Lucy Clarke
Colin Dayan
Daniel Morris
Petros Perros
(Jane Dickinson)
-----------------------------------------------------------------------------------------------------------------ABSTRACT OF PROPOSAL
A 1 year BOSU survey into dysthyroid optic neuropathy, epidemiology, presenting
features and current management.
Sight-threatening Graves’ orbitopathy (GO) / thyroid eye disease (TED) can be due
to one of 3 causes: a) dysthyroid optic neuropathy (DON); b) threatened or actual corneal
ulceration /perforation; and c) globe subluxation. This survey will focus on DON and its
typical presenting features as well current management throughout the UK.
DON is a rare major sight-threatening complication of Graves’ orbitopathy (GO). It
may be defined as impairment of optic nerve function caused by compression or stretch of
the optic nerve due to expansion of orbital tissues by inflammatory cells and
glycosaminoglycan deposition. It is observed in up to 5% of patients with GO. The
diagnosis is often challenging and management varies depending on the hospital, but
generally involves specialist ophthalmologists, ideally working in close liaison with
endocrinologists.
The aim of this survey is to determine incidence of DON; severity and associated
features on presentation; variations in management and outcomes at 9 months. It is the
first national epidemiological survey of DON and will help to determine the present scale
of this condition, how and by whom it is managed, and the spectrum of visual outcomes
after treatment.
-----------------------------------------------------------------------------------------------------------------PROPOSED STARTING DATE = Sept - Oct 2014
PROPOSED DURATION OF STUDY = 1 year
PROPOSED TERRITORIAL COVERAGE = Great Britain and Ireland
-----------------------------------------------------------------------------------------------------------------STATEMENT OF RESEARCH QUESTIONS
1) To estimate the incidence of DON within the British Isles.
2) To determine the constellation of features associated with DON.
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3) To determine variations in management strategies in DON.
4) To determine visual outcomes in treated DON.
-----------------------------------------------------------------------------------------------------------------GENERAL SUPPORTING STATEMENT
It has been estimated that DON may affect up to 5% of all patients with GO. For
patients with significant GO presenting to ophthalmologists the estimate is 10% (1), with a
higher prevalence in older male patients and those with concomitant vascular disease,
however recent evidence is emerging (unpublished EUGOGO data) that the incidence of
all forms of sight-threatening GO may be declining. There are two important reasons to try
to estimate the incidence of DON in the current UK population: firstly, a major
international initiative (the Amsterdam Declaration) is currently underway to improve
outcomes for patients with all forms of GO, and secondly, services for patients with sightthreatening GO are currently being developed as part of specialist commissioning. This
BOSU survey gives a unique opportunity to estimate the incidence of DON in Great Britain
and Ireland with reasonable confidence.
Accurate diagnosis of DON remains controversial as its definition has never been
universally agreed. A EUGOGO survey across Europe in 2007 (2) indicated that the most
useful clinical features are disc swelling, impaired colour vision and evidence of apical
crowding on imaging. Unfortunately no sign is consistently present (e.g. only 50% show
optic disc swelling) and the diagnosis currently rests on a constellation of features. It is
therefore of interest to determine the signs that prompt a diagnosis of DON and any
significant variations in this between clinicians. Additionally, data from outcomes of
intervention may give insight into which presenting features are of greatest clinical
relevance. These may include the importance of isolated defects on perimetry, and the
possible impact of ethnically determined orbital configuration.
There is currently no Gold Standard management protocol for DON and medical or
surgical treatment may be chosen. It would be of great interest to ascertain which initial
treatment is chosen and whether this depends on any local factors e.g. available surgical
expertise. A small previous study (3) suggests that there is a greater need for subsequent
medical treatment if surgery is chosen as the initial intervention than vice versa, and this
survey could help to confirm or refute that. In both instances this survey would give
valuable information on the final visual outcomes after treatment, about which there is
currently little known.
The results of this important survey would improve our understanding of DON and
potentially guide optimal future management, thus improving patient outcomes.
1)L Bartalena, A Pinchera, C Marcocci. Management of Graves' ophthalmopathy: reality
and perspectives. Endocrine Reviews 2000 21 168-199.
2) Clinical features of dysthyroid optic neuropathy: a European Group on Graves'
Orbitopathy (EUGOGO) survey. Br J Ophthalmol. 2007 Apr;91(4):455-8.
3) Wakelkamp IM, Baldeschi L, Saeed P, et al. Surgical or medical decompression as a
first-line treatment of optic neuropathy in Graves' ophthalmopathy? A randomized
controlled trial. Clin Endocrinol (Oxf). 2005;63(3):323-328.
-----------------------------------------------------------------------------------------------------------------2
STUDY METHODS
This is a prospective observational survey of DON over a 1 year period. Incident
cases will be identified via a questionnaire designed and reviewed by thyroid eye disease
experts. A second questionnaire at 9 months will review patient outcomes and should
hopefully highlight important management steps necessary for a good prognosis.
-----------------------------------------------------------------------------------------------------------------CASE DEFINITION AND INCLUSION CRITERIA
a) Graves orbitopathy:
For the purposes of this survey patients must have Graves’ orbitopathy which is defined as
an orbitopathy in the context of autoimmune thyroid disease. If any doubt exists there
should be evidence of thyroid dysfunction or thyroid autoimmunity.
b) Dysthyroid optic neuropathy (DON):
1) To meet the criteria for inclusion in this study, we have chosen to limit our definition of
DON to patients with 3 or more of the following features in at least one eye.

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Disc swelling
Impaired visual acuity (less than 6/6 or LOGMAR equivalent).
Impaired colour vision: at least 2 errors on testing with Ishihara or 1 error on HRR
plates (HRR plate numbers 5-9)
RAPD
Reproducible defect on automated perimetry in eyes with acuity of > 6/18
OR abnormal visual evoked potential (VEP)
Of course, none of these features should be used to define DON if due to alternative pathology.
2) If DON is diagnosed then for the patient to be included, it should be thought to be
reversible with treatment. For the purposes of this study, patients with DON of > 6
months duration should not be included.
3) A case of DON which has been reported to BOSU but which relapses during the followup period in the eye being treated should not be reported as a new case.
4) A case of DON newly affecting the second eye where the first eye was already reported
to BOSU and the patient is in the follow up period for the first eye should be reported
anew for the second eye.
REPORTING INSTRUCTIONS
All questionnaires should be returned in an envelope provided to Dr Yun Wong.
ETHICAL APPROVAL
Awaiting confirmation at the Royal Victoria Infirmary
Support from TEAMeD(UK) and BOPSS
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