It is important
to know the ocular manifestations of systemic diseases for
several reasons.
● Screening can detect early ocular changes that may require
treatment to prevent blindness.
A good example is a diabetic
patient with new vessels on the optic disc, which signal an
exceptionally high risk of visual loss unless treatment is
given in time.
● Knowledge of the ocular complications of other diseases may help in
the diagnosis of an ocular problem.
A red, locally injected, and
tender eye in a patient with rheumatoid arthritis suggests
scleritis, which may progress to perforation of the eye.
Iritis should be strongly considered in a young man with
ankylosing spondylitis who presents with a red eye.
● Ocular symptoms may suggest the systemic disease (for example,
prominent eyes and lid lag in hyperthyroidism) or confirm it
(for example, the Kayser-Fleischer ring of copper in Wilson’s
disease).
● Ocular signs may have prognostic value.
For example,
if cottonwool spots occur in the eyes of an
otherwise asymptomatic patient with AIDS, the prognosis
may be poor. Diabetes mellitus
Diabetes mellitus is the most common cause of blindness
among people of working age in the Western world.
Two per
cent of the diabetic population are blind, many of them in the
younger age groups.
Much of this eye disease can be treated,
which makes early identification and referral crucial.
Cataract and primary open angle glaucoma are more
common in diabetic than in non-diabetic patients.
Cataract
can be treated by surgical removal, and primary open angle
glaucoma can be treated by drugs and operations that lower
the intraocular pressure.
Cataract can often be detected by
viewing the red reflex; glaucoma by examining the optic
disc.
It is only too easy to forget to look for glaucomatous
cupping of the disc when looking for signs of diabetic
retinopathy.
Blinding diabetic retinopathy occurs in both insulin
dependent and non-insulin dependent diabetic patients of all
ages.
For all categories of patient, the longer the duration of
the diabetes, the more likely the patient is to have retinopathy
(about 80% are affected after 20 years).
However, the better the
control of blood sugar levels, the lower the incidence of
diabetic retinopathy. To avoid missing important signs, diabetic
patients should have their fundi examined annually, by dilating
the pupils with tropicamide 1%.
Non-proliferative diabetic retinopathy
This is typified by microaneurysms, dot haemorrhages, and
hard yellow exudates with well defined edges (called
background diabetic retinopathy in some classifications).
These
changes do not have much effect on vision when they occur in
the peripheral retina.
However, there is a spectrum of changes
in NPDR, some of which are associated with more ischaemic
damage.
These changes were previously classified as
“pre-proliferative” retinopathy.
The features of this more
ischaemic moderate to severe NPDR are:
● Intraretinal microvascular abnormalities (IRMA)
● Cottonwool spots
● Deeper blotch and cluster haemorrhages
● Venous dilatation, beading and looping.
NPDR may coexist with diabetic maculopathy.
The more
ischaemic NPDR changes should alert the clinician to the
possibility of progression to blinding proliferative diabetic
retinopathy.
Proliferative diabetic retinopathy
Typified by the growth of new vessels on the retina or into the
vitreous cavity and thought to result from the ischaemic
diabetic retina producing vasoproliferative factors that cause
the growth of abnormal new vessels.
These vessels may bleed,
causing a sudden decrease in vision because of a vitreous
haemorrhage.
Worse still, this blood often results in the
production of contractile membranes that gradually pull off the
retina (tractional retinal detachment), causing blindness.
This may occur in any diabetic patient, but more commonly is seen
in young, insulin dependent patients.
The vision may be 6/6
right up to the moment of a bleed, so early detection of new
vessels by adequate fundal examination is crucial.
Fluorescein
angiography may help to identify areas of retinal ischaemia and
new vessel formation.
New vessels may also grow at the front of
the eye on the iris and occlude the drainage angle of the
anterior chamber causing glaucoma (rubeotic glaucoma).
Laser treatment (or any other method of photocoagulation)
is used to treat proliferative retinopathy.
The laser, however, is
not usually used to coagulate new vessels as these may bleed or
recur.
When a patient has new vessels at the disc, the entire
retina is treated with laser, except for the macula area, which
preserves the central vision.
This treatment, often called
“panretinal photocoagulation” or “pattern bombing,” destroys
much of the ischaemic peripheral retina and stops it producing
the vasoproliferative factors that induce the growth of new
vessels, and often the new vessels regress.
New blood vessels on
the iris that block the outflow of aqueous and cause rubeotic
glaucoma may also regress.
However, thousands of laser burns
and repeated treatments may be needed to achieve this.
This treatment may substantially reduce peripheral vision and night
vision and means that the patient may have to give up driving.
There is much current research in the development of
clinically applicable antagonists to the vasoproliferative growth
factors (for example, vascular endothelial growth factor
(VEGF) antagonists).
Diabetic maculopathy
Diabetic maculopathy may be divided into four types:
● Focal exudative macular oedema
● Diffuse exudative macular oedema
● Ischaemic maculopathy
● Mixed types.
When diabetic retinopathy causes vessel leakage and ischaemia
in the macula area, central vision may be severely affected.
Diabetic maculopathy is the major cause of blindness in
maturity onset (Type 2) diabetes, but it also occurs in younger,
insulin dependent diabetics.
It may be amenable to focal laser
photocoagulation, which may help to reduce any leakage,
particularly when hard exudates are a prominent feature of the
maculopathy.
Screening for diabetic eye disease
Patients may be divided into five groups for screening purposes.
● Patients with no retinopathy or with minimal nonproliferative
(background) retinopathy and normal vision
when tested with glasses or pinhole.
These patients can be
reviewed yearly with dilation of the pupils. They should be
told to attend sooner if there is a change in vision that is not
corrected with glasses.
● Patients with non-proliferative (background) retinopathy and
changes around the macula area.
They should be referred to
an ophthalmologist, as this may herald a blinding
maculopathy.
● Patients with non-proliferative (background) retinopathy and
impaired acuity not corrected with glasses or pinhole.
The
patient may have an oedematous or ischaemic form of
maculopathy that is extremely hard to diagnose with the
direct ophthalmoscope alone.
The oedematous form may
respond to focal laser treatment if this is given early.
● Patients with moderate to severe non-proliferative
(preproliferative) retinopathy.
They have no new vessels, but
the haemorrhages are larger, the veins are tortuous, and
there are cottonwool spots.
These signs imply that the retina
is ischaemic and that there is a high risk that new vessels will
subsequently form. These patients should be referred.
● Patients with proliferative retinopathy.
This is typified
by new blood vessels, and sometimes cottonwool spots,
fibrosis, and vitreous haemorrhages. These patients need
immediate referral, particularly if there are vitreous
haemorrhages.
In addition to ocular treatment, blood sugar should be
carefully controlled.
If the blood sugar concentration is
brought under control rapidly, the fundus should be reviewed
regularly during this period, as there may be a transient
worsening of the retinopathy.
There is no question that good
control of the blood sugar level reduces diabetic retinopathy.
Hypertension, renal failure, and hyperlipidaemia worsen the
prognosis of retinopathy and must also be controlled.
Patients should be strongly advised not to smoke.
Diabetic patients are also more prone to recurrent corneal
abrasions, anteror uveitis, retinal vein occlusions, and cranial
nerve palsies.
Hypertension
The mild fundal changes of hypertension are extremely
common.
“Silver wiring” of the retinal arteries and
arteriovenous nipping are well known signs, but arteriolar
narrowing is the most reliable fundal sign.
Accelerated (malignant) hypertension is classically
associated with swelling of the head of the optic nerve.
Any
patient with hard exudates, cottonwool spots, or haemorrhages
as a result of hypertension has a grave prognosis.
Patients with
these fundal signs should have their blood pressure checked
and diabetes excluded.
Urgent referral to a physician is
required as this combination of signs may not only result in
blindness but is also life threatening.
Retinal vein occlusion is
also more common in hypertensive patients.
Thyroid eye disease
Patients may have signs associated with hyperthyroidism and
the consequent overaction of the sympathetic system.
These
patients have retracted upper and lower lids caused by excessive
stimulation of sympathetically innervated muscles in the
eyelids.
This also gives rise to the well known sign of lid lag
when the patient looks downwards.
These features may
suggest the diagnosis when the patient walks into the surgery.
If these signs are present, thyroid dysfunction should
be excluded.
If there are no visual problems, no corneal
exposure, and the eyes move normally the patient need not
be referred.
Patients may also have evidence of autoimmune disease
directed against the orbital contents, particularly the muscles
and orbital fat (thyroid autoantibodies may be positive).
These
signs may be associated with the classic signs of Graves’ disease,
including goitre, pseudoclubbing of the fingers (thyroid
acropathy), hyperthyroidism, and pretibial myxoedema.
Autoimmune orbital disease may also occur on its own with no
thyroid dysfunction and with normal thyroid autoantibody
status.
The clinical features include the following, which may
occur in any combination.
● Swelling of the eyelids
● Oedema (chemosis) and engorgement of the blood vessels of the
conjunctiva
● Exposure of the cornea because of lack of blinking and failure of
the lids to cover the eye adequately
● Pronounced protrusion (exophthalmos) of the eyes.
The absence of
this feature in association with the other features may be
even more serious, as a tight orbital septum may be holding
back the swollen orbital contents.
This may lead to a rise in
intraocular pressure as well as pressure on the optic nerve
● Restriction of eye movements.
This is caused by infiltration of the
muscles with inflammatory cells, and consequent
inflammation, oedema, and finally fibrosis.
These changes
can produce diplopia and strabismus
● Optic neuropathy.
This is relatively rare.
The fundal signs
include vascular congestion and swelling or atrophy of the
head of the optic nerve.
There may be “folds” in the choroid
caused by pressure on the globe. This should be excluded in
any patient with autoimmune eye disease who experiences
visual deterioration.
Management of thyroid eye disease
● Associated thyroid dysfunction should be excluded, although
treatment of any dysfunction may make no difference to the
eye disease, and it may even make it worse
● Patients should be strongly advised to stop smoking
● Artificial tears and ointments should be used to lubricate the
cornea and prevent drying and corneal ulceration (especially
at night)
● If there are cosmetic or exposure problems caused by lid
retraction, guanethidine 5% drops may reduce the lid
retraction by relaxing the sympathetically controlled retractor
muscles.
Occasionally an operation on these muscles may be
required
● If corneal exposure is threatening sight, the eyelids may have
to be sewn together temporarily or permanently
(tarsorrhaphy)
● Prisms incorporated in the patient’s glasses may help to
correct any double vision
● Operations on the muscles of eye movement may be required
to realign the eyes in patients with longstanding diplopia that
has stabilised.
Recently, the introduction of local injections of minute doses of botulinum toxin to paralyse specific
extraocular muscles has meant that patients with restrictive
muscle diseases may sometimes be treated at an earlier stage
● In serious disease with corneal problems or pressure on the
optic nerve, emergency treatment may be required, which
may include high doses of steroids, surgical orbital
compression, and radiotherapy.
The visual fields may be
restricted and there may be a relative afferent pupillary
defect
● Changes in colour vision, which may be noticed while
watching colour television, may be an important sign of optic
nerve compression, and patients should be told to inform
their doctor immediately if these changes are noticed
Rheumatoid arthritis
Ocular complications frequently occur in rheumatoid arthritis.
The lacrimal glands also are affected by an inflammatory
process with consequent inadequate tear flow.
The patient
complains of dry, gritty, and sore eyes.
Treatment consists of
replacement artificial tear drops instilled as often as necessary.
Simple ointment may also help, but this will blur the vision if
used during the day.
If there is an aggregation of mucus,
mucolytic eye drops (for example, acetylcysteine) may help, but
patients should be warned that these sting.
In a few patients the
“dry eye” syndrome may be sufficiently severe that there is
associated corneal melting.
The inflammatory process may also affect the episcleral and
scleral coats of the eye, causing the patient to complain of a
red, uncomfortable eye.
The redness is usually focal and there
is tenderness over the area.
Scleritis is usually much more painful than episcleritis and
the engorged vessels are deeper.
If scleritis continues, the sclera
may become thin (scleromalacia) and the eye may eventually
perforate.
The patient should be referred, as systemic
immunosuppression may be indicated.
These processes may also occur in other connective tissue
diseases such as systemic lupus erythematosus, scleroderma,
and dermatomyositis.
Seronegative arthritides
The seronegative arthritides include ankylosing spondylitis,
Reiter’s syndrome, psoriatic arthritis and arthritis associated
with inflammatory bowel disease.
Acute anterior uveitis (iritis,
iridocyclitis) is much more common in these patients.
If a
patient with any of these conditions has a red eye, anterior
uveitis should be suspected.
This is particularly true if the
patient has had past attacks, and “experienced” patients often
know when an attack is coming on.
The patient should be
referred for early treatment, which may prevent some of the
complications of anterior uveitis.
Seronegative childhood arthritis is a particularly important
cause of chronic anterior uveitis.
The great danger is that the
eyes in this condition are often white and pain free, and the
child may not complain of any visual problems.
There may be
secondary cataracts, which can cause irreversible amblyopia.
Glaucoma secondary to the anterior uveitis may also occur and
may be asymptomatic until the vision has been severely
damaged.
The group of children particularly at risk are girls,
those with fewer than five joints affected by the arthritis
(pauciarticular), and those with antinuclear antibodies in their blood.
These children should be referred to an
ophthalmologist.
Rosacea
Rosacea may seriously affect the eyes.
There is often associated
severe blepharitis, which may result in recurrent chalazia and
styes.
The abnormal lids and lipid secretion affect the tear film
and “dry eye” symptoms result.
The cornea scars, particularly
in the inferonasal and inferotemporal areas, with
neovascularisation.
Thinning occurs and occasionally the
cornea may perforate.
Treatment with tear substitutes is indicated together with
treatment for any associated blepharitis.
Systemic tetracycline
(250 mg four times daily for up to a month, then daily for
several months) may considerably improve the patient’s ocular
as well as facial condition (avoid using tetracycline in pregnant
or lactating women).
Sarcoid
Sarcoid is associated with various ocular problems.
Acute uveitis
and chronic uveitis occur, which may result in cataract,
glaucoma, and a band of calcium deposited in the cornea
(band keratopathy).
The lacrimal glands may be infiltrated,
resulting in “dry eye” symptoms that require tear replacement.
The granulomatous process may affect the posterior part of the
eye as vasculitis and sometimes infiltration of the optic nerve.
Congenital rubella
The ocular manifestations of congenital rubella are extremely
important.
The child may have severe learning difficulties and
be deaf, so early recognition of ocular problems and their
treatment are vital.
The eyes are often microphthalmic and
associated treatable defects include cataract, glaucoma, squint,
and refractive errors.
The cataract may not appear until several
weeks or months after birth, so the eyes should be re-examined.
There may be a diffuse retinopathy (“salt and pepper”
appearance).
Acquired immune deficiency
syndrome (AIDS)
The ocular complications of AIDS can be blinding and include
retinitis, retinal detachment, papillitis, and cystoid macular
oedema.
Manifestations of ocular human immunodeficiency
virus (HIV) infection include Kaposi’s sarcoma of the
conjunctiva and lids, HIV microvasculopathy (retinal
haemorrhages and cottonwool spots), and vasculitis.
Ocular
cytomegalovirus (CMV) infection presents as a slowly
progressive necrotising retinitis with areas of retinal
opacification and haemorrhages and exudates along the
vascular arcades.
About 20-30% of patients with CMV retinitis
will develop a retinal detachment.
Various antiviral agents have proved useful in the treatment
of ocular complications, but they may have to be taken
continuously, and systemic side effects from these treatments
are common.
The use of agents such as ganciclovir, foscarnet,
cidofovir, and more recently fomivirsen has proved to be very
effective in controlling CMV retinitis.
Intraocular implants that
release local antiviral agents reduce systemic complications.
Blindness resulting from the ocular complications of AIDS used
to be one of the major reasons for suicide in AIDS patients.
The development of highly active antiretroviral therapy
(HAART), with combinations of drugs including nucleoside
reverse transcriptase inhibitors, non-nucleoside reverse
transcriptase inhibitors, and protease inhibitors has
dramatically reduced the incidence of ocular CMV infection.
Advances in therapy now result in improved immune
function in many AIDS patients and new ophthalmic
manifestations of AIDS are emerging.
These include
inflammation of the vitreous (vitritis) and accumulation of
fluid at the macula (cystoid macular oedema).
