Scleritis : Clinical features, treatment and systemic associations

continuing education
19
Scleritis: Clinical features, treatment
and systemic associations
Robert Petrarca describes the various presentations of a significant
cause of eye pain, and reviews the many systemic associations with
the condition (C3656, one standard point)
Successful participation in each module
counts as one credit towards the GOC CET
scheme administered by Vantage and one
towards the AOI’s scheme.
INFLAMMATION OF THE SCLERA
ocular pressure. It consists almost entirely
includes a wide spectrum of conditions, of collagen bundles with some elastin,
ranging from benign self-limiting episodes
proteoglycans and glycoprotein.
to severe necrotising processes.
Anteriorly, the sclera merges with the
The estimated prevalence in the
cornea, creating the internal scleral sulcus
general population is 3-10 per 10,000.1 occupied by the trabecular meshwork.
Establishing the correct diagnosis at
Posteriorly, the sclera merges with the
presentation is essential, as the future
dura mater and arachnoid sheaths of the
management, prognosis and compli- optic nerve as it exits the globe. Here the
cations are very different. The first
sclera forms the lamina cribrosa, which has mation of the sclera tends to be painful
important differentiation to make as
a sieve-like structure, providing support
due to its rich nerve supply, pain being
a clinician is between episcleritis and
for the perforating optic nerve fibres.
triggered by the direct stimulation of
scleritis, as episcleritis rarely requires
The blood supply of the sclera is
nerve endings or stretching of the nerves
treatment, while scleral diseases almost
derived from the anterior and posterior
from tissue swelling and infiltration. Also,
always require systemic therapy.
ciliary arteries forming the three identi- as the extraocular muscles insert into the
Generally, the correct diagnosis
fiable vascular layers over the anterior
sclera, the pain is often made worse with
requires a detailed history and a careful
sclera. The requirements are low because
eye movement.
ocular examination, to determine which
of the slow collagen and cell turnover of
The sclera is particularly prone to
layers of the sclera are inflamed.
the tissue.
inflammation because of its unique
The classification of scleral inflamSensory innervation of the posterior
anatomy and vascular characteristics,
mation was devised at Moorfields Eye
sclera is via short posterior ciliary nerves, which allow transudation into the tissue.
Hospital (Table 1). It is based on the
which enter the sclera around the optic
However, there is a slow clearance,
anatomical site and the severity of the
nerve, while the long posterior ciliary
allowing intense immune reactions to
disease at presentation.2 It is particularly nerves supply the anterior sclera. Inflam- occur and persist.3 There are three vascular
useful because most patients remain
layers covering the anterior sclera and
TABLE 1
in the same clinical class throughout
it is important to understand these
the course of their disease.
layers to reliably differentiate scleritis
Classification and referral guideline for optometrists
from episcleritis (Figure 1).
ANATOMY
(a)
Posterior scleritis
(b)
Same day to A&E
Same day to A&E
Immediate referral
1 Conjunctival plexus, which is the
most superficial consisting of
tortuous fine vessels that are movable
over the underlying structures
2 Superficial episcleral plexus within
Tenon’s capsule where the vessels
are radially arranged. Site of episcleritis
Less urgent
May be routinely
referred
Immediate referral
(c)
FIGURE 1. (a) Normal (b) Episcleritis (c) Scleritis. Courtesy of J Kanski, Clinical Ophthalmology 4th Edition, Butterworth-Heinemann
www.opticianonline.net
M ,  N  V  Optician
▲
The sclera is the main outer protective coat of the eye and, along with
the cornea, protects the intraocular
structures from injury and displacement. Its mechanical strength is
important for maintaining the shape
of the eye and containing the intra-
Diffuse anterior scleritis
Nodular anterior scleritis
Anterior necrotising with
inflammation
Scleromalacia perforans
continuing education
20 SCLERITIS
Anterior necrotising scleritis with
inflammation
FIGURE 2a
FIGURE 2b
3 Scleral plexus, which lies deep to Tenon’s
capsule and directly above the sclera. Site
of scleritis.
The diagnosis of scleritis is based on the
presence of scleral oedema and congestion of the scleral plexus. The inflamed
area may take on a deep purple shade
under daylight. The use of 10 per cent
phenylephrine will cause blanching of
the two superficial layers in episcleritis,
but will have no effect on the deep scleral
plexus during scleritis. There may also be
congestion of the superficial vessels, but
this should be ignored.
CLINICAL FEATURES
This is the most common form characterised by widespread inflammation
involving a sector or the entire anterior
sclera (Figures 2a and 2b). There is
marked oedema of both the episcleral
and scleral tissue leading to distortion of
the normal radial vessel pattern which
becomes engorged and tortuous. As the
scleral tissues become stretched, the
accompanying nerves are stimulated,
causing severe pain. This is characteristically referred to the brow and jaw and
reaches its peak in five to 10 days.4
Nodular anterior scleritis
Here the inflammation is limited to a
well-defined area on the sclera such that
distinct immobile nodules result, usually
found in the interpalpebral region close
to the limbus (Figure 3). The adjacent
episclera is often swollen and may
resemble nodular episcleritis except that
the scleral nodule is fixed and cannot be
moved over the underlying tissue, and is
tender to palpation.
Optician M ,  N  V 
FIGURE 3
enlarge and represent areas of infarcted
sclera surrounded by thinned scleral
tissue, eventually leaving a thin layer of
fibrous tissue over exposed choroid and
formation of staphylomas. These areas
appear blue/black in colour and have a
dramatic appearance; however, unless the
intraocular pressure rises significantly, the
risk of perforation is rare and no treatment
is required or effective7 (Figure 6).
Posterior scleritis
Posterior scleritis is inflammation of the
sclera posterior to the ora serrata, involving
the choroid, retina and optic nerve. It is
an uncommon and under-recognised
condition. However, the increasing use
of B-mode ultrasonography has revealed
that posterior scleritis occurs much more
frequently than previously thought and
can lead to rapid and permanent visual
loss. It may present with a range of clinical
findings, depending on the location,
extent and severity of the inflammation.9
Patients commonly present with
symptoms of periocular pain, reduced
vision, pain on eye movement and it is
often associated with anterior scleritis.
Physical signs are often diverse and
variable, but most commonly include
a swollen optic disc, choroidal folds,
serous retinal detachment, sub-retinal
Anterior necrotising scleritis
without inflammation
Otherwise known as scleromalacia
perforans, it is a rare form of anterior
scleritis and usually affects women with
long-standing rheumatoid arthritis with
extra-articular manifestations.1
The eye is rarely uncomfortable, unlike
necrotising scleritis with inflammation.
Patients instead present having either
noticed an abnormal appearance in their
sclera, or with blurred vision from astigmatism induced by the scleral thinning.6
The signs to be observed on examination start with the presence of asymptomatic yellow/grey patches in an otherwise
uninflamed sclera. These patches are
necrotic areas of sclera caused by obliterative
arteritis involving the deep scleral plexus.8
The necrotic areas continue to
FIGURE 4a. (J Kanski, Clinical Ophthalmology 4th
Edition, Butterworth-Heinemann)
FIGURE 4b. (J Kanski, Clinical Ophthalmology 4th
Edition, Butterworth-Heinemann)
www.opticianonline.net
▲
Diffuse anterior scleritis
This is the most severe and destructive
form of scleral inflammation. Therefore,
when a patient first presents with
symptoms and signs consistent with this
disease, all initial examinations of the eye
must be focused on discovering whether
necrosis is present.
The onset of pain and localised redness
may at first be gradual, however within
three to four days, extremely severe and
persistent pain has usually developed,
radiating to the patient’s temple, brow or
jaw. It characteristically worsens at night,
keeping the patient awake, producing
great anxiety and distress. 5
During the development of this
condition, there are several signs to be
observed. Initially, the scleritis develops
in a localised area with acute congestion of
the vessels within the deep scleral plexus.
Blood in the vessels overlying the affected
area becomes static, causing vascular
distortion and occlusion (Figures 4a and
4b), leading to an avascular patch with
capillary non-perfusion and infarction of
the episclera (Figure 5a).
As a consequence, necrosis of the
involved sclera develops, leading to loss
of tissue and ulceration of the overlying
conjunctiva. If the inflammation remains
uncontrolled, adjoining areas of scleritis
may coalesce, leaving the area extremely
thin and translucent, exposing the brown
colour of the uvea underneath. 6
Serious complications are rare until
the necrotising scleritis has become
almost circumferential and inflammation
has spread to the adjacent structures of
the cornea, ciliary body and trabecular
meshwork. Raised intraocular pressure
above 40mmHg can lead to staphylomas
developing and rarely perforation (Figure
5b). Long-standing uveitis may be complicated by secondary cataract, glaucoma and
macular oedema.7
continuing education
22 SCLERITIS
FIGURE 5a
FIGURE 5b
masses and raised intraocular pressure.
However, in 17 per cent of patients there
are no detectable physical signs of disease.
Other reported signs include lid oedema,
lid retraction, proptosis, ophthalmoplegia
and, rarely, angle-closure glaucoma.9
Diffuse and nodular posterior
scleritis
Ultrasonography is the key investigation
to make the diagnosis of posterior scleritis
and classification entirely depends on
the ultrasound appearance. This shows
thickening of the posterior sclera and a
clear zone immediately posterior to the
globe, which is fluid in Tenon’s space
causing separation and the characteristic
‘T’ sign appearance (Figure 7).
It is also possible with ultrasonography to
differentiate between diffuse and nodular
posterior scleritis. Additional investigations
with CT scanning and fluorescein angiography are rarely needed except for confirmation in uncertain cases.
Posterior necrotising scleritis
Histopathological studies have reported
that necrotising posterior scleritis does
rarely occur. However, ultrasonography
is currently unable to differentiate it
from diffuse scleritis. As the early signs
of necrotising inflammation such as
ischaemia and thinning cannot be visualised, it is most frequently being discovered
incidentally by vitreo-retinal surgeons.9
associated with systemic disorders in 40 per
cent of patients, scleromalacia perforans in
70 per cent and necrotising with inflammation in 95 per cent of cases.10 In the
majority, the systemic disease would
have previously been diagnosed. The
main exception being systemic vasculitis
which, given its potential life-threatening
course, should be ruled out.11 In posterior
scleritis, 29 per cent of patients have an
associated systemic disease, with the
associations being similar to those found
in anterior scleritis.9
Rheumatoid arthritis is the most
common systemic condition associated
with scleritis, typically seen in women
in the sixth decade of life. Up to 33 per
cent of all patients with scleritis will
be suffering from rheumatoid arthritis,
while the incidence of scleritis in arthritic
patients is only approximately 6 per cent.
The most common presentation is as
diffuse anterior scleritis. However, this
depends on the onset in the course of the
systemic disease. Scleritis developing
early is usually of the diffuse or nodular
presentation, while patients with longstanding rheumatoid arthritis have a much
greater chance of developing necrotising
scleritis along with the worst visual
prognosis. Presentation for the first time
in patients older than 60 also indicates a
poorer prognosis with the development
of necrotising scleritis, decreases in vision
and peripheral ulcerative keratitis. Finally,
scleromalacia perforans has a very strong
association with long-standing rheumatoid arthritis.1,12,13,14
Wegener’s granulomatosis is the
most common vasculitis associated with
scleritis. It is a multisystem disorder,
characterised by the triad of necrotising
granulomatous inflammation of the upper
and lower respiratory tracts, systemic
vasculitis and glomerulonephritis. Ocular
complications occur in up to 58 per cent
of patients and can be the presenting sign
in 16 per cent of undiagnosed patients.
Most commonly, Wegener’s will be associated with diffuse and nodular scleritis.
However, necrotising scleritis and peripheral corneal inflammation may also occur,
which is a significant threat to vision,
requiring aggressive immunosuppressive
therapy (Figure 8).15,16
Systemic lupus erythematosus (SLE)
SYSTEMIC ASSOCIATIONS
Optician M ,  N  V 
FIGURE 7. (J Kanski, Clinical Ophthalmology 4th
Edition, Butterworth-Heinemann)
is a chronic systemic immunologicallymediated disease of unknown aetiology,
with a wide range of presentations.
Scleritis is often directly related to the
deterioration of the systemic disease.
Presenting as anterior diffuse or nodular
disease and in patients with anticardiolipin antibodies as posterior scleritis.17
Polyarteritis nodosa is a non-granulomatous necrotising vasculitis of small
and medium-sized vessels. Ocular
involvement can be seen in 20 per cent
of patients, usually affecting the retinal
and choroidal circulation. Rarely scleritis
is present and has an appearance similar
to Wegener’s granulomatosis.18 In both
polyarteritis nodosa and SLE the scleritis
may be relatively painless.
Takayasu’s arteritis is a granulomatous necrotising vasculitis of large-sized
arteries, particularly the aortic arch and
its branches. Anterior scleritis has been
reported as the initial manifestation.19
Infection is the cause of 7.5 per cent
of cases of scleritis and can be caused
by viruses, bacteria, fungi and parasites,
the most frequent being herpes zoster
ophthalmicus which accounts for half the
cases.20
TREATMENT AND MANAGEMENT
Following the investigation and diagnosis
of scleritis, aggressive therapy is needed
to prevent complications that can occur
in the later stages of the disease. Associations with underlying systemic diseases
and infections make it one of the most
challenging conditions to manage in
ophthalmology.
Anterior non-necrotising scleritis
The initial treatment for diffuse and
nodular scleritis should always be
systemic non-steroidal anti-inflammatory drugs (NSAIDs). These include
the non-selective cox inhibitors, flurbiprofen, indomethacin and ibuprofen.
The new selective cox-2 inhibitors have
been reported to be equally successful
and minimise the side effects. However,
no clinical trials have been conducted.
Patients given high doses of NSAIDs
should be warned of potential side effects
including gastrointestinal irritability and
bleeding, skin rashes, renal and hepatic
toxicity and drug interactions.21
Over 90 per cent of patients with diffuse
www.opticianonline.net
▲
A large number of systemic diseases have
been associated with scleral disease and
over the years it has become apparent that
scleritis may represent the initial manifestations of an undiagnosed systemic
disease. The diffuse and nodular types are
FIGURE 6
continuing education
26 SCLERITIS
MULTIPLE-CHOICE QUESTIONS
1 The vascular layer involved in scleritis is:
A Limbal plexus
B Conjunctival plexus
C Superficial episcleral plexus
D Scleral plexus
FIGURE 8
or nodular scleritis treated with a NSAID
will achieve control of the inflammation,
while the addition of steroids or immunosuppressants will control the inflammation
in most of the remaining cases.22
Necrotising and posterior scleritis
Corticosteroids such as prednisolone are
the first line treatment for patients with
necrotising and posterior scleritis. They
are the gold standard to which other
therapies are compared. They are administered in high doses either orally or intravenously to achieve disease remission.
Oral corticosteroids are started at high
doses between 60-80mg/day in adults and
then tapered to an acceptable maintenance dose. Intravenous corticosteroids
are used when rapid remission is required
for patients with necrotising scleritis with
potential globe perforation. Short-term
therapy with high-dose corticosteroids
are generally well tolerated, however, high
doses given over a prolonged period are
associated with significant side effects.22
Immunosuppressive
agents
are
indicated for patients with severe scleritis,
in situations where corticosteroids are
inadequate to control disease or when the
dose is too high to be tolerated for long
term treatment (Table 2).
TABLE 2. Immunosuppresants
Cyclosporine
Azathioprine
Methotrexate
Cyclophosphamide
Mycophenolate mofetil
CONCLUSION
Scleritis can be a severe ocular condition
with significant complications and
patients being difficult to diagnose
and manage. Therefore, establishing
the correct diagnosis at presentation is
essential, requiring a detailed history and
careful ocular examination. Treatment
must be specific for the patient and
monitored regularly to balance the
benefits of long-term therapy against
intolerable side effects.
Acknowledgement
Professor Miles Stanford, Professor of Ophthalmology at St Thomas’ Hospital, London.
Optician M ,  N  V 
4 The most common systemic disease
associated with scleritis is:
A Osteoarthritis
B Rheumatoid arthritis
C Systemic lupus erythematosus
D Wegener’s granulomatosis
2 Scleritis is diagnosed by:
A Deep purple shade and congestion of the
episcleral plexus
B The presence of scleral oedema and
congestion of the episcleral plexus
C The presence of scleral oedema and
congestion of the sclera plexus
D Congestion of the superficial vessels
5 Which of the following is not a
recognised treatment for scleritis
A Indomethacin
B Prednisolone
C Cyclophosamide
D Diphenhydramide
3 Necrotising scleritis is associated with a
systemic disease in:
A 16% of cases
B 40% of cases
C 70% of cases
D 95% of cases
6 In practice you see a patient you
suspect of having anterior necrotising
scleritis with inflammation. A suitable
management decision would be:
A Immediate referral
B Same day to A&E
C Routinely referred
D Review in a week
The deadline for response is April 27
Module C3656 To take part in this CET module go to www.opticianonline.net
and click on the Continuing Education section. Successful participation counts
as one credit towards the GOC CET scheme administered by Vantage and
one credit towards the Association of Optometrists Ireland’s scheme.
References
1 McGavin DD, Williamson J, Forrester JV, et al.
Episcleritis and scleritis: a study of their clinical
manifestations and association with rheumatoid
arthritis. Br J Ophthalmol, 1976;60:192-226.
2 Watson PG, Hayreh SS. Scleritis and episcleritis.
BMJ, 1976;60:163-191.
3 Watson PG, Young RD. Scleral structure, organisation and disease. A review. Experimental Eye Research,
2004;78:609-623.
4 Jones WL. Diseases of the sclera. In: Clinical ocular
pharmacology. Bartlett JD, Jaanus SD. 4th ed, Boston,
2001;701-713.
5 Sainz de la Maza M and Foster CS. Scleritis and
episcleritis. In: Oxford textbook of ophthalmology. Easty
DL and Sparrow JM, eds. Vol 1. Oxford: Oxford
Medical Publications, 1999;347-354.
6 Watson PG. Classification of scleral inflammation.
In: Scleritis: Fundamentals of clinical ophthalmology.
McCluskey P. London, BMJ Books, 2001;19-27.
7 Lightman S. Complications of scleritis. In: Scleritis:
Fundamentals of clinical ophthalmology. McCluskey P.
London, BMJ Books, 2001;91-100.
8 Mader TH, Stulting RD, Crosswell HH. Bilateral
paralimbal scleromalacia perforans. Am J Ophthalmol,
1990;109:233-234.
9 McCluskey PJ, Watson PG, Lightman et al.
Posterior scleritis: clinical features, systemic associations and outcome in a large series of patients.
Ophthalmology, 1999;106:2380-2386.
10 Pavesio CE, Meier FM. Systemic disorders
associated with episcleritis and scleritis. Curr Opin
Ophthalmol, 2001;12:471-478.
11 Akpek EK, Thorne JE, Qazi FA et al. Evaluation of patients with scleritis for systemic disease.
Ophthalmology, 2004;111:501-506.
12 Sainz de la Maza M, Escobar BJL, Foster CS.
Characteristics of scleritis in patients older than 60
years. Archivos de la Sociedad Espanola de Oftalmología,
2001;76:425-430.
13 Pavesio CE, Meier FM. Systemic disorders
associated with episcleritis and scleritis. Curr Opin
Ophthalmol, 2001;12:471-478.
14 Sainz de la Maza M, Foster CS, Jabbur NS.
Scleritis associated with rheumatoid arthritis and
with other systemic immune-mediated disease.
Ophthalmology, 1994;101:1281-1286.
15 Sainz de la Maza M, Foster CS, Jabbur NS.
Scleritis associated with systemic vasculitic diseases.
Ophthalmology, 1995;102:687-692
16 Hakin KN, Watson PG. Systemic associations of
scleritis. Int Ophthalmol Clin, 1991;31:111-129.
17 Muserocchi E, Baltatzia S, Foster CS. Ocular
features associated with anticardiolipin antibodies:
a descriptive study. Am J Ophthalmol, 2001;131:
451-456.
18 Akova YA, Jabbur NS, Foster CS. Ocular presentation of polyarteritis nodosa: clinical course and
management with steroid and cytotoxic therapy.
Ophthalmology, 1993;100:1775-1781.
19 Jain R, Ionides A, Pavesio C, et al. Scleritis as
a presenting feature of Takayasu’s disease. Br J
Ophthalmol, 2000;84:801.
20 Jabs DA, Mudun A, Dunn JP, et al. Episcleritis
and scleritis: clinical features and treatment results.
Am J Ophthalmol, 2000;130:469-476.
21 Wakefield D, McCluskey P. Investigation and
management of scleritis. In: Scleritis: Fundamentals
of clinical ophthalmology. McCluskey P. London, BMJ
Books, 2001;101-116.
22 Saintz de la Maza M, Jabbur NS, Foster CS.
An analysis of therapeutic decisions for scleritis.
Ophthalmology, 1993;100:1372-1376.
◆ Robert Petrarca is a medical student at
Guy’s, King’s & St Thomas’ Medical School,
London and an optometrist in private
practice
www.opticianonline.net