a term correctly used to describe inflammation of the uveal tract
(iris, ciliary body, choroid) alone, in reality comprises a large
group of diverse diseases affecting not only the uvea but also the
retina, optic nerve and vitreous. Uveitis is a major cause of severe
visual impairment and has been estimated to account for 10-15% of
all cases of total blindness in the USA. In surveys of the causes
of blindness uveitis has usually not been included and is probably
threatening complications include: cystoid macular oedema, secondary
glaucoma, secondary cataract, vitreous opacities and retinal scars.
The majority of patients are of working age and so this condition
may cause potentially serious economic consequences with many days
off work or job losses as well as interfere with education and prevent
International Uveitis Study Group classification separates uveitis
by anatomical localisation of the disease, according to the major
visible signs: anterior, posterior, pan and intermediate. The course
of the disease can be described as acute, chronic (> 3 months
duration) and recurrent. In the majority of cases of endogenous
uveitis, the aetiology is unknown although some cases are a manifestation
of a systemic disease, such as sarcoidosis or Behçet's disease,
whilst others are associated with the HLA-B27 related group of diseases.
Although one can attach a label to a number of uveitis syndromes,
such as Fuchs' heterochromic cyclitis or Vogt-Koyanagi-Harada (VKH)
disease their underlying cause is unknown. Despite this, classifying
uveitis patients into different subgroups is important, even if
an aetiology is never found, as evidence exists on how best to manage
these distinct uveitis entities and their likely prognoses.
of the most pressing questions that arises in the mind of every
ophthalmologist who sees a new case of uveitis is "what is the cause
of this disease?" In evaluating patients with uveitis, the ophthalmologist
must consider that a lengthy list of infections, autoimmune systemic
diseases, distinctive inflammatory conditions and masquerade syndromes
may all cause uveal inflammation. Despite this array of potential
diagnoses, the vast majority of patients have disease that defies
most uveitis patients routine serological and radiological investigations
are usually unhelpful. There are no serological markers of disease
activity as can be found in patients with systemic vasculitis. Also,
any abnormalities found in peripheral blood are unlikely to reflect
what is going on inside the eye. Nevertheless, because uveitis has
a puzzling nature and it may form part of a systemic disease process,
many patients are frequently over-investigated by being subjected
to a battery of unnecessary tests.
management of uveitis should be a systematic approach tailored to
each patient's particular type of uveitis. It is essential that
a detailed history is taken and direct questioning should include
asking about back / joint problems, skin disease, respiratory disease,
neurological disease, gastrointestinal disease, mouth and genital
ulcers and sexually transmitted disease. When seeing a patient with
chronic or recurrent disease it is important to pay attention to
previous findings in the notes for any clues to diagnosis, such
as an absence of posterior synechiae in a white and painless eye
(Fuchs' heterochromic cyclitis), or unilateral uveitis often associated
with raised intraocular pressure recurring within a few months of
stopping topical steroids (herpes simplex or varicella zoster uveitis).
A careful ocular examination should be performed as details such
as conjunctival or iris nodules or iris atrophy may point to a specific
diagnosis. It is often the history and examination findings that
are far more informative than any laboratory investigations and
may save the patient undergoing unnecessary investigations. Most
patients do not have an underlying systemic disease.
no large studies exist which demonstrate the value of investigating
patients with uveitis. A number of specific uveitis entities can
often be diagnosed solely on clinical examination; these include
Fuchs' heterochromic cyclitis and recurrence of presumed congenital
ocular toxoplasmosis, neither of which require further investigations.
exists as to whether patients with the commonest type of uveitis
(acute anterior uveitis - AAU) should be investigated. It is well
recognised that approximately 50% of patients with AAU are HLA-B27
positive. A number of these patients will give a history of an associated
HLA-B27 disease. In the others, HLA typing is unnecessary because
the result will not help in the future management of the patient.
Also, HLA-B27-associated AAU often presents with a number of clinical
clues which help in diagnosis: it is usually recurrent, unilateral
but alternating, with severe anterior chamber inflammation (posterior
synechiae, fibrin and hypopyon).
is important to understand the reasons for ordering any investigation:
it identify any underlying systemic disease process or association?
it provide a 'definitive' aetiology?
it confirm or reject a diagnosis?
it help in the management of the patient?
of results is also very important, particularly with regards to
false negatives and false positives. The latter are not uncommon
with regards to syphilis serology and the Mantoux test.
retrospective review of patients with various types of uveitis showed
the following abnormal results: full blood count: 23/113 (20.3%),
plasma viscosity / ESR: 37/108 (34.2%), VDRL/TPHA: 3/70 (4.3%),
angiotensin converting enzyme (ACE): 9/77 (10.8%) and chest x-ray
(CXR): 15/103 (14.6%). Sarcoidosis was diagnosed in eight patients
who had an abnormal CXR ± raised ACE. None of the other abnormal
results helped in establishing an underlying cause for the uveitis
or assisted in the further management of the patients. All patients
with symptoms of other organ system dysfunction or general malaise
should be investigated to rule out under-lying systemic disease.
large numbers of tests in the hope that one may turn out to be positive
should be actively discouraged. If one does enough investigations
on any patient there is the chance that something will turn up abnormal
but it may have no relevance to the uveitis.
should be paid to the sensitivity and specificity of each test:
- measures how well the presence of a disease is predicted by
a diagnostic test.
- measures how well the absence of a disease is predicted by a
the clinical setting, the minimum number of investigations should
be performed that will give the maximum information regarding the
management of the patient. There are a number of general tests that
would be common to most uveitis patients, and specific tests that
might be relevant to a particular type of uveitis.
blood count (eosinophilia in parasitic infections, raised white
count in bacterial infections, relative lymphocytosis in viral infections
viscosity/ESR (underlying systemic disease)
x-ray (CXR) (sarcoidosis and tuberculosis)
other tests that need to be ordered should depend on the clinical
findings and the ophthalmologist's index of suspicion for a particular
joint x-ray (HLA-B27 related disease)
converting enzyme (ACE) (sarcoidosis)
dye test / IgG antibodies (if negative in undiluted serum to exclude
typing (birdshot retinochoroidopathy)
cytoplasmic antibody (Wegener's granulomatosis)
test (tuberculosis, may be negative in sarcoidosis)
fluorescein angiography (AMMPE, geographic choroidopathy)
scan of chest (sarcoidosis)
scan of orbits / B-scan ultrasound (posterior scleritis)
head scan (demyelination, non-Hodgkins lymphoma,
studies (demyelination, non-Hodgkins lymphoma, VKH)
biopsy (sarcoidosis-'blind' biopsies should be discouraged)
chain reaction of intraocular fluid (herpesviral DNA, propionibacter
biopsy (non-Hodgkins lymphoma, amyloid)
biopsy (non-Hodgkins lymphoma)
"immunological" tests are often of little help. Out of a series
of 893 uveitis patients screened for a variety of non-ocular specific
autoantibodies, the only significant finding was in patients with
juvenile chronic arthritis in whom 10/13 (77%) were antinuclear
some patients with recurrent or chronic uveitis, repeating investigations
3-5 years later may increase the yield of positive results. Those
patients in whom an underlying systemic disease is suspected should
be referred to a Physician as they may require more detailed/invasive
is a puzzling and potentially sight threatening disease. Do not
expect to find a 'definitive' aetiology in the vast majority of
patients. A detailed history and thorough clinical examination remains
essential in establishing a diagnosis of underlying systemic disease
in these patients. Baseline screening investigations should be avoided
as they do not contribute to finding a cause or help in management,
and are often expensive. Tests should be tailored to the clinical
findings and ordered only if there is a strong suspicion of systemic
I. Murray PhD FRCS FRCOphth
Professor of Ophthalmology
University of Birmingham
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