Uveitis

UVEITIS

Inflammation of the uvea) )

Anatomy of the uvea(uveal tract):

Uvea is the vascular middle coat(layer) of the eyeball.
Anatomical regions of the uvea(from Anterior to Posterior):
1.the iris(anterior uvea)
2.the ciliary body(intermediate uvea)
(pars plicata-anteriorly- and pars plana-posteriorly-)
3.the choroid(posterior uvea)

Uveitis

Uveitis is the most common disorder of the uvea.
Classification of uveitis:

Anatomical classification

1
Uveitis, by strict definition implies an inflammation of the uveal tract. However, the term is commonly used to describe many forms of intraocular inflammation involving not only the uvea but also the retina and its vessels.

2
Anterior uveitis may be subdivided into:


•
Iritis in which the inflammation primarily involves the iris.

•
Iridocyclitis in which both the iris and the pars plicata of the ciliary body are involved.

3

Intermediate uveitis is defined as inflammation predominantly involving the pars plana, the peripheral retina and the vitreous.

4
Posterior uveitis involves the fundus posterior to the vitreous base.

•

Retinitis with the primary focus in the retina.

•
Choroiditis with the primary focus in the choroid.

•
Vasculitis which may involve veins, arteries or both.


5
Panuveitis implies involvement of the entire uveal tract without a predominant site of inflammation.

Anatomical classification:

1.Anterior uveitis(iritis or iridocyclitis)
2.itermediate uveitis(cyclitis)
3.posterior uveitis(choroiditis)
4.panuveitis(involve all the 3 regions of the uvea)

B.Clinical classification:

1.acute uveitis
2.chronic uveitis

Etiology:

(causes of uveitis)

1.idiopathic:

In about 50% of the cases of uveitis

2.infectious causes:

a. Bacteria: T.B. , syphilis, leprosy.
b.Viruses: HSV, VZV, Cytomegalovirus.
c.Fungi: candidiasis, Aspergillosis.
d.Parasites: toxoplasmosis, histoplasmosis.

3.non-infectious causes : (systemic inflammatory disease)
a. Behcet disease
b. ankylosing spondylitis
c.sarcoidosis
d.inflmmatory bowel disease( Crohn's disease, ulcerative colitis)
e.psoriatic arthritis
f.juvenile rheumatoid arthritis

4.other causes:

a.post-operatively; after any intra-ocular surgery such as cataract or glaucoma.
b.immuno-compromised patient e.g. AIDS
c.exposure to toxins, medications, intra-ocular foreign bodies.

Clinical Features:

Based on anatomical classification;

A. anterior uveitis:

a ===== Acute anterior uveitis

Anterior uveitis is the most common form of uveitis. Acute anterior uveitis (AAU) is the most common form of anterior uveitis, accounting for three-quarters of cases. It is characterized by sudden onset and duration of 3 months or less. It is easily recognized due to the severity of symptoms which will force the patient to seek medical attention.

1

Presentation is typically with sudden onset of unilateral pain, photophobia and redness, which may be associated with lacrimation. Occasionally patients may notice mild ocular discomfort a few days before the acute attack when clinical signs are absent.

2
Visual acuity is usually good at presentation except in eyes with severe hypopyon.

3
External examination shows ciliary (circumcorneal) injection which has a violaceous hue .

4
Miosis due to sphincter spasm may predispose to the formation of posterior synechiae unless the pupil is pharmacologically dilated.

5
KPs are clusters of cellular deposits on the corneal endothelium composed of epithelioid cells, lymphocytes and polymorphs .


6
Aqueous cells (cells in AC[Anterior Chamber] ) indicate disease activity and their number reflects disease severity .

7

Anterior vitreous cells indicate iridocyclitis.

8
Aqueous flare reflects the presence of protein in AC due to a breakdown of the blood–aqueous barrier .

9

Aqueous fibrinous exudate typically occurs in HLA-B27-associated AAU .

10
Hypopyon (pus in AC) is a feature of intense inflammation in which cells settle in the inferior part of the anterior chamber (AC) and form a horizontal level .

11

Posterior synechiae (adhesions between the iris and anterior capsule of the lens) may develop quickly and must be broken down before they become permanent .

12
Low intraocular pressure (IOP) may occur as a result of reduced secretion of aqueous by the ciliary epithelium. Occasionally the intraocular pressure may be elevated (hypertensive uveitis) as in herpetic uveitis .

13
Fundus examination is usually normal, but should always be performed to exclude ‘spillover’ anterior uveitis associated with a posterior focus, notably toxoplasmosis .

14
Duration. With appropriate therapy the inflammation tends to completely resolve within 5–6 weeks.

15
The prognosis is usually very good. Complications and poor visual prognosis are related to delayed or inadequate management. Steroid-induced hypertension may occur but glaucomatous damage is uncommon.


b ===== Chronic anterior uveitis
Chronic anterior uveitis (CAU) is less common than the acute type and is characterized by persistent inflammation that promptly relapses, in less than 3 months, after discontinuation of treatment. The inflammation may be granulomatous or non-granulomatous. Bilateral involvement is more common than in AAU.

1

Presentation is often insidious and many patients are asymptomatic until the development of complications such as cataract or band keratopathy. Because of the lack of symptoms patients at risk of developing CAU should be routinely screened; this applies particularly in patients with juvenile idiopathic arthritis.

2
External examination usually shows a white eye. Occasionally the eye may be pink during periods of severe exacerbation of inflammatory activity.

3
Aqueous cells vary in number according to disease activity but even patients with numerous cells may have no symptoms.

4
Aqueous flare may be more marked than cells in eyes with prolonged activity and its severity may act as an indicator of disease activity (contrary to previous teaching).

5
KPs are clusters of cellular deposits on the corneal endothelium composed of epithelioid cells, lymphocytes and polymorphs .

6

Dilated iris vessels (pseudorubeosis) are occasionally seen in long-standing cases and resolve with treatment.

7
Iris nodules typically occur in granulomatous disease.


8
Iris atrophy that is sectoral occurs characteristically in herpes simplex and herpes zoster .
.

9
The duration is prolonged and in some cases the inflammation may last for many months or even years. Remissions and exacerbations of inflammatory activity are common and it is difficult to determine when the natural course of the disease has come to an end.

Intermediate uveitis

Presentatio: are usually floaters with or without impairment of vision.
Signs:
---cellular infiltration of the vitreous (vitritis) with fewer cells in AC.
---normal fundus.

C.Posterior uveitis

Posterior uveitis encompasses retinitis, choroiditis and retinal vasculitis. Some lesions may originate primarily in the retina or choroid but often there is involvement of both (retinochoroiditis and chorioretinitis).

1

Presentation varies according to the location of the inflammatory focus and the presence of vitritis. For example a patient with a peripheral lesion may complain of floaters whereas a patient with a lesion involving the macula will predominantly complain of impaired central vision.

2
Retinitis (inflammation of the retina) may be focal (solitary), multifocal, geographic or diffuse.


3
Choroiditis (inflammation of the choroid) may also be focal, multifocal, geographic or diffuse. I Active choroiditis is characterized by a round, yellow nodule .

4
Vasculitis may occur as a primary condition or as a secondary phenomenon adjacent to a focus of retinitis. Both arteries (periarteritis) and veins (periphlebitis) may be affected although venous involvement is more common. Active vasculitis is characterized by yellowish or grey-white, patchy, perivascular cuffing that may be associated with haemorrhage. Quiescent vasculitis may leave perivascular scarring, which should not be mistaken for active disease.

The Treatment

The Aims of Treating Uveitis:

1.To prevent vision-threatening complications.

2.To relieve the patients discomfort.
3.To treat the underlying disease, if possible.

Principles of treatment

General principles
Treatment of immune-mediated uveitis involves predominantly the use of anti-inflammatory and immunosuppressive agents. Antibiotic therapy for infectious diseases . It is important to keep in mind that drugs used to treat uveitis have potential side-effects, and this should always be weighed against the decision to treat. Also, it must be emphasized that the use of systemic therapy should be carried out in conjunction with a physician who is competent to deal with complications associated with both the underlying disease and the therapy.
Mydriatics
Preparations

1

Short-acting


a
Tropicamide (0.5% and 1%) has a duration of 6 hours.

b
Cyclopentolate (0.5% and 1%) has a duration of 24 hours.

c
Phenylephrine (2.5% and 10%) has a duration of 3 hours but no cycloplegia.

2

Long-acting

a

Homatropine 2% has a duration of up to 2 days.

b
Atropine 1% is the most powerful cycloplegic and mydriatic with a duration of up to 2 weeks.

Indications

1
To promote comfort by relieving spasm of the ciliary muscle and pupillary sphincter.

2
To break down recently formed posterior synechiae .

3
To prevent formation of posterior synechiae .


STROIDS

Topical steroids

Indications

1

Treatment of AAU is usually relatively straightforward.

•

Initial therapy involves instillation either hourly or even more frequently according to severity of inflammation.

•
Once the inflammation is controlled the frequency should be carefully tapered to 2-hourly, followed by 3-hourly, then four times a day and eventually reduced by one drop a week. The drops are often discontinued altogether by 5–6 weeks.

2

Treatment of CAU is more difficult because long-term therapy is often required with the risk of complications such as cataract and steroid-induced elevation of intraocular pressure.

•

Exacerbations are initially treated in the same way as acute anterior uveitis. If the inflammation is controlled with no more than +1 aqueous cells, the rate of instillation can be gradually further reduced by one drop/month.

•
The classical teaching that only cellular reaction in the anterior chamber represents active inflammation has been challenged. Flare is caused by chronic break-down of the blood–aqueous barrier, but the intensity of the flare can also indicate an active process, which may respond to therapy.

•
Following cessation of treatment, the patient should be re-examined within a short time to ensure that the uveitis has not recurred.


Complications

1

Elevation of IOP is common in susceptible individuals (‘steroid responders’), but long-term exposure to topical steroids may eventually result in glaucoma in many patients.

2
Cataract can be induced by both systemic and, less frequently, topical steroid administration. The risk increases with dose and duration of therapy.

3
Corneal complications, which are uncommon, include secondary infection with bacteria and fungi, recrudescence of herpes simplex keratitis, and corneal melting, which may be enhanced by inhibition of collagen synthesis.

4
Systemic side-effects are rare, but may occasionally occur following prolonged administration, particularly in children.
Periocular steroid injection

1

Advantages over topical administration

•

Therapeutic concentrations behind the lens may be achieved.

•
Water-soluble drugs, incapable of penetrating the cornea when given topically, can enter the eye trans-sclerally when given by periocular injection.

•
A prolonged effect can be achieved with ‘depot’ preparation such as triamcinolone acetonide (Kenalog) or methylprednisolone acetate (Depomedrone).


2
Indications

•

In unilateral or asymmetrical intermediate or posterior uveitis, periocular injections should be considered as first-line therapy to control inflammation and macular oedema.

•
In bilateral posterior uveitis either to supplement systemic therapy or when systemic steroids are contraindicated.

•
Poor compliance with topical or systemic medication.

•
At the time of surgery in eyes with uveitis.

3

Complications

•

Globe penetration.

•
Elevation of IOP, which with depot preparations may be refractory.

•
Ptosis.

•
Subdermal fat atrophy.

•
Extraocular muscle paresis.

•
Optic nerve injury.

•
Retinal and choroidal vascular occlusion.

•
Cutaneous hypopigmentation.


Intraocular steroids

1

Injection

•

Triamcinolone acetonide (4 mg in 0.1 mL) is an option in the treatment of posterior uveitis and CMO unresponsive to other forms of therapy.

•
It produces rapid resolution of CMO lasting about 4 months and may be used to determine reversibility of visual loss due to CMO.

•
Injections may be used following surgery on eyes with uveitis when other forms of prophylaxis are not appropriate.

•
Complications include elevation of IOP, cataract, endophthalmitis (sterile or infectious), haemorrhage and retinal detachment.

2

Slow-release implants appear to be useful in patients with posterior uveitis who do not respond to, or are intolerant to, conventional treatment.

•

The implant, either a biodegradable insert or a slow-release reservoir (fluocinolone acetonide, dexamethasone), is implanted via a pars plana incision.

•
The steroid is continuously released for 18 months–3 years and this may obviate the use of long-term systemic steroids.

•
Complications are similar to those of intravitreal triamcinolone injection.


Systemic steroids

1

Preparations

a

Oral prednisolone 5 or 25 mg tablets are the main preparations.

b
Intravenous infusion of methylprednisolone 1 g/day, repeated for 2 to 3 days is an option in severe disease.

2

Indications

•

Intermediate uveitis unresponsive to posterior sub-Tenon injections.

•
Sight-threatening posterior or panuveitis, particularly with bilateral involvement.

•
Rarely, anterior uveitis resistant to topical therapy.

•
Occasionally prior to intraocular surgery as prophylaxis against worsening inflammation.


3
Contraindications

•

Poorly controlled diabetes is a relative contraindication.

•
Peptic ulceration.

•
Osteoporosis.

•
Active systemic infection.

•
Psychosis on previous exposure to steroids.

4

General rules of administration


•
Start with a large dose and then reduce.

•
The starting dose of prednisolone is 1–2 mg/kg/day given in a single morning dose, after breakfast.

•
A high level is maintained until a clinical effect is seen, followed by a slow taper over several weeks to avoid reactivation.

•
Doses of 40 mg or less for 3 weeks or less do not require gradual reduction.

•
Doses of more than 15 mg/day are unacceptable long-term so that the use of a steroid-sparing agent has to be considered. A common cause of failure of treatment is sub-optimal dosage.

5

Side-effects depend on the duration and dose of administration.

a

Short-term therapy may cause dyspepsia, mental changes, electrolyte imbalance, aseptic necrosis of the head of the femur and, very rarely, hyperosmolar hyperglycaemic non-ketotic coma.

b
Long-term therapy may cause a Cushingoid state, osteoporosis, limitation of growth in children, reactivation of infections such as TB, cataract and exacerbation of pre-existing conditions such as diabetes and myopathy. Rarely, systemic steroids may cause severe ocular hypertension in children, even when administered only for several days.


Antimetabolites
Indications

1

Sight-threatening uveitis, which is usually bilateral, non-infectious, reversible and has failed to respond to adequate steroid therapy.

2
Steroid-sparing therapy in patients with intolerable side-effects from systemic steroids or those with chronic relapsing disease requiring a daily dose of prednisolone of more than 10 mg. Once a patient has been started on an immunosuppressive drug and the appropriate dose ascertained, treatment should continue for 6–24 months, after which gradual tapering and discontinuation of medication should be attempted over the next 3–12 months. However, some patients may require long-term therapy for control of disease activity.

Methotrexate, Azathioprine, Mycophenolate, Ciclosporine, Tacrolimus.

Biological blockers
The exact indications and efficacy of these drugs in the treatment of uveitis are largely unknown although there are several clinical trials currently in progress. The two main groups are:

1

Interleukin receptor antagonists such as daclizumab and anakinra.

2
Tumour necrosis factor alpha antagonists such as infliximab and adalimumab.