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 underestimated.
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 driving.
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 categorisation.
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:
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.
identify any underlying systemic disease process or association?
provide a 'definitive' aetiology?
confirm or reject a diagnosis?
help in the management of the patient?
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:
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.
- measures how well the presence of a disease is predicted by a diagnostic
- measures how well the absence of a disease is predicted by a diagnostic
count (eosinophilia in parasitic infections, raised white count in bacterial
infections, relative lymphocytosis in viral infections or tuberculosis)
tests that need to be ordered should depend on the clinical findings and
the ophthalmologist's index of suspicion for a particular diagnosis.
viscosity/ESR (underlying systemic disease)
x-ray (CXR) (sarcoidosis and tuberculosis)
"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 antibody positive.
joint x-ray (HLA-B27 related disease)
converting enzyme (ACE) (sarcoidosis)
dye test / IgG antibodies (if negative in undiluted serum to exclude congenital
typing (birdshot retinochoroidopathy)
cytoplasmic antibody (Wegener's granulomatosis)
test (tuberculosis, may be negative in sarcoidosis)
fluorescein angiography (AMMPE, geographic choroidopathy)
of chest (sarcoidosis)
of orbits / B-scan ultrasound (posterior scleritis)
scan (demyelination, non-Hodgkins lymphoma,
(demyelination, non-Hodgkins lymphoma, VKH)
biopsy (sarcoidosis-'blind' biopsies should be discouraged)
chain reaction of intraocular fluid (herpesviral DNA, propionibacter DNA)
biopsy (non-Hodgkins lymphoma, amyloid)
biopsy (non-Hodgkins lymphoma)
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 investigations.
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 disease.
I. Murray PhD FRCS FRCOphth
GR, Flynn TE. Syphilis exposure in patients with uveitis. Ophthalmology
JE, Stavrou P, Moradi P, Murray PI. Should we investigate patients with
uveitis? Invest Ophthalmol Vis Sci 1998;39:S608.
P. Serum autoantibodies and uveitis. Br J Ophthalmol 1986;70:266-8.
PI, Stavrou P, Marr JE, Moradi P. Pattern of visual loss in patients
with uveitis. Invest Ophthalmol Vis Sci 1998;39:S607.
JT, Wernick R. The utility of routine screening of patients with uveitis
for systemic lupus erythematosus or tuberculosis. A Bayesian analysis.
Arch Ophthalmol 1990;108:1291-3.
A, Suttorp-van Schulten MS, Frits Treffers W, Kijlstra A. Causes and
frequency of blindness in patients with intraocular inflammatory disease.
Br J Ophthalmol 1996;80:332-6.
Schulten MSA, Rothova A. The possible impact of uveitis in blindness:
a literature survey. Br J Ophthalmol 1996;80:844-8.