Intraocular Inflammation

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10 Intraocular Inflammation

The uveal tract consists of the iris, ciliary body and choroid lying in continuity; inflammation in this tract is known as uveitis. Uveitis can be classified according to the principal site of inflammation as anterior uveitis, intermediate uveitis (a subgroup of which is pars planitis), posterior uveitis or panuveitis. Because the uveal tract is continuous, severe inflammation in one part may be accompanied by signs of overspill inflammation in another. For example, a severe anterior uveitis (iritis) may be accompanied by a cellular infiltrate in the anterior vitreous (some ophthalmologists would term this an iridocyclitis). Conversely, posterior uveitis may be accompanied by signs of inflammation in the anterior chamber; furthermore, diseases included under the umbrella of posterior uveitis often have significant retinal signs.

The onset of uveitis may be acute or chronic, defined as inflammation continuing for more than 3 months. Acute inflammation produces pain, redness and photophobia and sometimes blurring of vision, depending on the degree of haze within the ocular media. Chronic inflammation occurs in a whiter eye, but clinical appearances may change with time so that acute symptoms may be followed by chronic uveitis and vice versa. Granulomatous uveitis is differentiated from the nongranulomatous type by the appearance of the keratic precipitates (KPs). In granulomatous uveitis, KPs have a large pale greasy appearance (mutton fat KP) and the eye is generally not particularly red. Mutton fat KP used to be taken to indicate that the uveitis was caused by a systemic granulomatous disease such as sarcoidosis or tuberculosis but this clinical distinction is blurred as many of these patients have no detectable underlying systemic disease. Furthermore, there is often considerable overlap in the appearance of KPs with granulomatous diseases such as sarcoidosis sometimes presenting with nongranulomatous KPs whereas nongranulomatous diseases such as multiple sclerosis can present with granulomatous KPs.

Whilst uveitis is often thought of as a distinct entity, a secondary uveitis frequently plays an important role in many other ocular diseases such as corneal infection, scleritis and ocular trauma or in surgery, where it is responsible for many postoperative complications. Uveitis produces visual loss through cataract or loss of clarity of the ocular media, glaucoma, hypotony from defective secretion of aqueous humour, retinal or choroidal destruction, macular oedema or neovascularization.

The eye has a number of particularly unusual immunological features. The avascularity of the cornea, vitreous and lens and the physiological blood–aqueous and blood–retina barriers normally isolate the eye from the general immune system. There is no intraocular lymphatic drainage, so that any ocular immune response must be mediated through the blood. The immune privilege enjoyed by the eye is maintained by active immunosuppression. Resident support cells in the retina such as astrocytes and Müller cells also have a role in immune surveillance being able to present antigen, to phagocytose and to participate in healing and scarring.

Anterior and posterior uveitis appear to be entirely different diseases. Anterior uveitis is associated with a wide variety of systemic stimuli (e.g. ankylosing spondylitis, urethritis, inflammatory bowel disease) in which the initial immune event appears to be extraocular and then becomes targeted on the eye; circumstantial evidence suggests a role for autoimmune cross-reactivity between bowel flora and ocular antigens. Posterior uveitis is thought to be an example of an organ-specific disease mediated by T cells reactive to one or more specific antigens derived from the retina. The discovery that a retinal protein (S antigen) could induce a retinochoroiditis has led to great advances in the understanding of the mechanisms of posterior uveitis in experimental animals although the application to human disease has so far been disappointing. Several other retinal proteins such as rhodopsin, opsonin and interphotoreceptor retinol binding protein have also been found to be uveitogenic.

SIGNS OF UVEITIS

Inflammation within the eye causes damage to the vascular endothelium of the intraocular vessels with consequent breakdown of the blood–ocular barriers and exudation of leucocytes and proteins into the eye. The signs of this process within the eye will depend on the region most affected, the rapidity of onset, its severity and duration.

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Fig. 10.14 Macular oedema can be seen with posterior uveitis of any type or severity; it is the most common cause of visual loss, although mild degrees can be compatible with normal visual acuity. Depending on the duration and severity of inflammation, the oedema resolves with the uveitis leaving a normal macula or progresses to permanent retinal damage. Macular oedema is often difficult to visualize ophthalmoscopically unless the macula is viewed stereoscopically with a fundus lens (see Ch. 1). Fluorescein angiography can be very useful in its assessment. In mild cases leakage will be seen from the parafoveal retinal capillaries; in more established cases there is pooling of fluorescein within the intraretinal cystoid spaces, giving a petalloid appearance to the angiogram. This patient with mild posterior uveitis had an acuity of 20/60, biomicroscopy showed macular thickening and fluorescein angiography shows marked macular oedema. Optical coherence tomography (OCT) clearly shows the intraretinal cystic spaces and macular thickening.

ANTERIOR UVEITIS

ACUTE ANTERIOR UVEITIS

Acute anterior uveitis (AAU) is the most common type of uveitis with an incidence of about 15 per 100000 population per year. About 50 per cent of patients are HLA-B27 positive compared with about 8 per cent of the normal population. However, other factors are important in the pathogenesis, as 25 per cent of patients with ankylosing spondylitis (more than 90 per cent of whom are HLA-B27 positive) will suffer an attack of anterior uveitis during their lifetime compared with only 1 per cent of a normal population with HLA-B27. Being HLA-B27 positive correlates with uniocular involvement, increased severity and joint disease, especially in men but otherwise there are no special features that distinguish HLA-B27-positive from HLA-B27-negative patients. Common systemic associations of AAU are ankylosing spondylitis, psoriatic arthropathy and Reiter’s syndrome, all also linked to HLA-B27. There are many other associations of AAU but these are uncommon and, in the absence of any systemic signs or symptoms, it is reasonable to restrict the investigation of a new patient to a blood count and chest radiography. More extensive investigations should be reserved for patients with symptoms of systemic disease or an atypical course.

Herpes zoster ophthalmicus

Keratitis (see Ch. 4) and anterior uveitis are common features of herpes zoster ophthalmicus and may occur independently of each other. It is said that keratitis and uveitis are particularly frequent if the vesicles appear along the side of the nose, the cutaneous distribution of the nasociliary nerve that also innervates the iris and pupil but this is not invariably so.

The uveitis is frequently subacute in onset and is often associated with keratitis. It may persist for many months. Sector atrophy of the iris is commonly seen and is due to an occlusive vasculitis of the iris vessels; retroillumination of the iris shows sectorial translucency to advantage. Corneal anaesthesia is commonly present and persists. Ocular nerve palsies and optic neuritis are occasionally seen and post-herpetic neuralgia can be disabling in a minority of patients. Oral antiviral agents should be given in the acute vesicular cutaneous stage of the disease. The rash heals more quickly with less post-herpetic neuralgia and a lower incidence of ocular involvement. The severity of the cutaneous disease does not necessarily correlate with the degree of severity of ocular involvement. Herpes zoster in young patients may indicate an underlying systemic immunosuppressive illness such as human immunodeficiency virus (HIV) infection or malignancy.

CHRONIC ANTERIOR UVEITIS

Juvenile idiopathic arthritis

Juvenile idiopathic arthritis can be divided into three main subtypes according to the presenting pattern of joint disease. These are the systemic, polyarticular and pauciarticular types. Ocular involvement is seen most commonly in the latter group, particularly in girls, and especially if antinuclear antibodies are present. HLA-DR5 carries an increased risk of ocular involvement. Occasionally the uveitis may precede joint symptoms by up to 2 years. Conversely development of uveitis after 5 years of joint disease is unusual. Typically the ocular disease is bilateral and the eye is completely white and painless. Accordingly there is a need to screen such children on a regular basis, particularly those at high risk. Visual loss occurs from band keratopathy, glaucoma or cataract. Many patients can be treated by topical or local steroid orbital injections; methotrexate is useful to control both the arthritis and eye disease without the problems of growth retardation from systemic steroids. Cataract surgery is frequently required; IOL implantation remains highly controversial in these children and at present is probably best avoided. Secondary glaucoma is a serious complication that responds poorly to standard medical treatment; surgical drainage with antimetabolites has considerably improved the prognosis.

Fuchs’ heterochromic cyclitis

This is a distinctive entity with many features not seen with other forms of uveitis. Small diffuse KPs are scattered over the whole of the corneal endothelium with a fluffy or feathery appearance of their border in contrast to the well circumscribed and inferiorly sited KPs seen with other types of uveitis. The eye is white and posterior synechiae do not form. The iris has a characteristic moth-eaten appearance and becomes de-pigmented, showing a bluish tinge in Caucasian patients. This depigmentation is not as obvious in heavily pigmented eyes where iris stromal atrophy is the hallmark. Heterochromic cyclitis is usually unilateral although bilateral cases rarely occur and are more difficult to diagnose. Glaucoma may develop and is associated with a fine neovascularization of the iris and angle (see Ch. 8). Cataracts are common and are hastened by steroid therapy; the benefit of steroids in this condition is unproven. Histopathological examination of iris specimens shows stromal atrophy with loss of pigment, hyalinization of blood vessel walls, proliferation of vascular endothelial cells and patchy loss of pigment epithelium. There is an inflammatory cell infiltrate of eosinophils, mast cells, lymphocytes and plasma cells; Russell bodies (immunoglobulins) are present. Recent evidence suggests that the condition is due to persistent localized rubella viral infection.

INTERMEDIATE UVEITIS

This usually affects young adults. It is usually bilateral and starts insidiously. Patients have white eyes and present with floaters from vitreous debris or blurred vision of gradual onset from macular oedema. Most cases have no apparent aetiology, but there is a well recognized association with multiple sclerosis and similar findings may occasionally be seen in patients with sarcoidosis. Anterior segment inflammation is minimal. A cellular vitreous infiltrate is always present in the anterior vitreous gel, together with snowballs (accumulations of cells), which are usually seen inferiorly in the peripheral vitreous gel. A low-grade peripheral periphlebitis is sometimes present. A ‘snowbank’ is a massive infiltrate that is sometimes seen inferiorly over the inferior pars plana and peripheral retina by scleral indentation; these patients are said to have pars planitis. The snowbank is composed of collagen, fibroblasts and astrocytes with an inflammatory cell infiltrate. It is sometimes associated with fibroglial membranes and neovascularization. Macular oedema and mild optic disc swelling are common. Neovascularization of the optic disc or peripheral retina may occur in some eyes. Most patients have a good visual prognosis with the disease burning out over a number of years. The most common cause of visual loss is macular oedema and occasionally vitreous haemorrhage or retinal detachment (from an associated posterior vitreous detachment). In some patients intermediate uveitis is associated with multiple sclerosis which may either precede or succeed the diagnosis of ocular inflammation.