Ankylosing spondylitis

About 50 per cent of Caucasian patients who are HLA-B27 positive will have some signs of ankylosing spondylitis. Young adult males are predominantly affected with a male:female ratio of 3:1. Attacks of anterior uveitis occur acutely, usually in one eye and are not related to exacerbations of joint disease, its severity or any other known predisposing factor. The attacks usually subside over 4–6 weeks with treatment and with prompt treatment do not tend to cause residual ocular damage. Most patients can expect several attacks of acute anterior uveitis in either eye before the disease burns out in later life but the degree to which any one patient is affected is extremely variable. There is evidence that immune cross-reactivity to bowel flora may have a pathogenetic role.

Fig. 10.15 About 50 per cent of HLA-B27-positive patients will have evidence of ankylosing spondylitis which is seen in its earliest form in the sacroiliac joints. There is sclerosis of the periarticular bone with narrowing and irregularity of the joint space, progressing eventually to ankylosis. Similar changes are seen in the spine.

Fig. 10.16 This patient has the typical kyphoscoliotic posture of ankylosing spondylitis. He has had a total hip replacement for ankylosis of the joint. Note the swelling of the right knee and the deformity of the feet.

Reiter’s syndrome

This syndrome is a triad of arthritis, urethritis or dysentery, and acute anterior uveitis. Typically a seronegative (i.e. rheumatoid factor negative) arthritis affecting large peripheral joints such as the knees and the sacroiliac joints follows a few weeks after bacterial dysentery or a nonspecific urethritis. Conjunctivitis and uveitis occur in 30–50 per cent of patients. Other systemic features are plantar fasciitis and keratoderma blennorhagica on the penis, palms or soles of the feet. Aortic incompetence is a rare late complication. Males are usually affected; HLA-B27 is virtually always present and there is evidence that the disease is related to chlamydial genital infection if it follows a nonspecific urethritis. Partial manifestations of the syndrome are common. In most patients the uveitis recovers over a few weeks but the arthritis can progress to chronic joint destruction.

Fig. 10.17 Typical keratoderma blennorhagica of the penis.

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.

Fig. 10.18 Herpes zoster ophthalmicus with involvement of the nasociliary nerve along the lateral border of the nose. Cutaneous lesions may vary in severity from confluent vesicles to the occasional punctate lesion.

Fig. 10.19 Sectorial iris atrophy following herpes zoster uveitis. Retroillumination of the iris would show loss of iris pigment epithelium.

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.

Fig. 10.20 This little girl aged 4 years with pauciarticular disease has a swollen right knee on which she cannot weight bear.

By courtesy of Dr B Ansell.

Fig. 10.21 Typical features of chronic anterior uveitis in juvenile idiopathic arthritis. There is a moderately advanced band keratopathy with posterior synechiae and a dense cataract. There is no conjunctival injection.

By courtesy of Mr J Kanski.

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.

Fig. 10.22 The right eye of this patient is normal but the left shows stromal atrophy consistent with Fuchs’ heterochromic cyclitis. The left iris has a slightly bluish tinge. Note the peripheral iridectomy from previous glaucoma surgery.

Fig. 10.23 In African Caribbean patients, heterochromia is not seen and iris stromal atrophy is the hallmark. Superficial nodules can be seen on the stromal surface in some patients.

Fig. 10.24 This photograph shows the typical KPs of Fuch’s heterochromic cyclitis. These cover the whole of the endothelial surface and have ‘spidery’ margins. A stringy cellular infiltrate can often be seen in the vitreous.

By courtesy of Mr K Barton.

Multiple sclerosis

Many patients with optic neuritis have a subclinical low-grade peripheral periphlebitis (Rucker’s lines) that resolves spon-taneously. The association between intermediate uveitis and multiple sclerosis is well recognized; some patients develop neurological symptoms many years after the onset of their eye problems. Patients with multiple sclerosis may also develop granulomatous panuveitis.

Fig. 10.27 Low-grade subclinical periphlebitis is a common finding in patients presenting with acute optic neuritis.

Sarcoidosis

Sarcoidosis is responsible for about 5 per cent of all cases of anterior uveitis and is also a common cause of posterior uveitis. It is a multisystem disorder and ocular involvement of some type (which may be the presenting feature) is seen in about 25 per cent of all patients with systemic disease. About 75 per cent of patients presenting with ocular sarcoidosis will have positive chest radiographic findings: bilateral hilar lymphadenopathy in the acute form and pulmonary interstitial fibrosis in the chronic stage. Although chest radiographic changes provide good circumstantial evidence of sarcoidosis the diagnosis should be confirmed histologically where possible by demonstrating noncaseating granulomas in biopsy tissue. The serum level of angiotensin-converting enzyme is frequently raised in patients with systemic sarcoidosis and, although not specific to this disease, this is a useful diagnostic pointer in patients presenting with uveitis. It can also act as a marker of disease activity and response to treatment. The Kviem test is now obsolete.

Anterior uveitis, panuveitis and posterior uveitis with retinal vasculitis are the most common features of ocular sarcoidosis. The anterior uveitis may be acute or chronic and either granulomatous or nongranulomatous. Patients with acute sarcoidosis and bilateral hilar lymphadenopathy with erythema nodosum tend to present with acute ocular inflammation, whereas those with more chronic systemic disease normally have less acute ocular signs. Patients should be examined for evidence of granulomas in other common sites such as the lacrimal glands, eyelids or conjunctiva. Biopsy in these areas is easy to perform and confirms the diagnosis.

Fig. 10.28 Positive findings of sarcoidosis are found on chest radiography in about 75 per cent of patients, especially in those with recent onset of the disease. These patients may have erythema nodosum. Computed tomography shows the pulmonary changes in better detail. Bronchoscopy, bronchial lavage and biopsy can be useful to confirm the diagnosis. Hilar lymphadenopathy usually resolves spontaneously but systemic steroid therapy may be indicated in the presence of pulmonary interstitial fibrosis.

Fig. 10.29 This 28-year-old woman presented with acute AAU, bilateral hilar lymphadenopathy and erythema nodosum on her legs.

Fig. 10.30 Radioactive gallium is taken up by macrophages in granulomas (not only with sarcoidosis) and can be used to demonstrate the extent of systemic involvement with sarcoidosis. This patient shows uptake in the lacrimal glands, nasopharynx and chest.

Fig. 10.31 Sarcoid granulomas in this patient are seen along the lid margin and on the tarsal conjunctiva. ‘Blind’ biopsy of normal appearing conjunctiva with multiple sections will sometimes demonstrate noncaseating granulomas.

Fig. 10.32 Lacrimal gland infiltration is common. The gland must be biopsied transcutaneously to avoid damaging the conjunctival ductules and exacerbating the risk of a dry eye. Sarcoidosis is particularly common in African Caribbean patients.

Fig. 10.33 Biopsy of the lacrimal gland shows the typical appearances with a large noncaseating granuloma containing multinucleated giant cells.

Fig. 10.34 Retinal vasculitis and posterior uveitis can occur in the absence of anterior uveitis; localised areas of focal periphlebitis in the small peripheral retinal veins are almost pathognomic of sarcoidosis. Typically a creamy white infiltrate ‘candle wax’ is seen around the equatorial retinal veins.

Fig. 10.35 More subtle changes may be observed on fluorescein angiography. This 45-year-old woman presented with a low-grade posterior uveitis. Focal periphlebitis can be seen on the angiogram, suggesting that the patient has sarcoid.

Fig. 10.36 Major venous occlusions, such as central retinal vein occlusion are rare but severe periphlebitis can lead to vascular occlusion and peripheral vascular closure, which may be followed by neovascularization at the border of perfused and nonperfused retina. Neovascularization may also occur at the optic disc. It is amenable to photocoagulation of the areas of capillary closure provided that intraocular inflammation has been adequately suppressed before treatment.

Fig. 10.37 Optic disc swelling may result from local oedema with posterior uveitis, local infiltration with sarcoid granulomata, optic nerve compression by a granuloma at the orbital apex or, occasionally, from raised intracranial pressure with neurosarcoid. Chronic optic nerve infiltration can cause optic atrophy in the absence of disc swelling. This patient with neurosarcoid has a massive granuloma of the disc.

Fig. 10.38 Focal atrophic retinal pigment epithelial (RPE) changes are often seen in the inferior fundus, particularly in middle-aged and elderly women with long-standing disease. They are due to granulomatous change in the RPE or choroid. Initially the lesions have a fluffy creamy appearance that resolves to leave atrophic RPE changes.

Fig. 10.39 Granulomas may be seen on the trabecular meshwork in ocular sarcoid. They can lead to secondary glaucoma from peripheral anterior synechiae.

Behçet’s disease

Behçet’s disease was originally described in males of Eastern Mediterranean origin but is increasingly recognized, often in less dramatic forms, in females and other racial groups. The diagnosis is made clinically and is based on the triad of uveitis, oral and genital ulceration. The clinical signs are divided into major criteria of mouth or genital ulceration, uveitis and skin lesions (erythema nodosum, thrombophlebitis, folliculitis) and minor criteria such as arthritis, gastrointestinal ulceration, venous occlusions and neurological signs. The aetiology of Behçet’s disease is unknown. Ocular involvement is particularly related to the presence of the HLA-B51 antigen which has a prevalence of about 60 per cent in most populations studied.

Behçet’s disease carries a poorer visual prognosis than almost any other form of posterior uveitis. Many patients will respond to systemic steroids but cytotoxic treatment is indicated in patients with severe ocular disease. Cyclosporin A is very useful in the management of these patients although the drug itself carries a risk of systemic toxicity and withdrawal of treatment may cause a florid relapse of uveitis. Mycophenolate mofetil is less toxic and an increasing range of newer immunologically based treatments such as interferon and anti-tumour necrosis factor α drugs are becoming available; these agents are likely to have an increasing impact in the management of severe disease.

Fig. 10.40 Mouth ulcers are painful and episodic and cannot be distinguished clinically or pathologically from aphthous ulceration. Their presence often predates ocular symptoms sometimes by many years.

Fig. 10.41 Genital ulcers are not seen as frequently as mouth ulcers. This patient has active ulceration but white scars can be seen at sites of previous ulceration.

Fig. 10.42 Recurrent hypopyon is a widely recognized feature of severe Behçet’s disease. There is a brisk cellular reaction in the anterior chamber often with a surprising lack of conjunctival injection. Patients with disease that is confined to the anterior segment alone have a better prognosis.

Fig. 10.43 The posterior uveitis of Behçet’s disease may be asymmetrical or even unilateral. There is usually diffuse vascular leakage throughout the fundus; focal periphlebitis (as seen in sarcoidosis) is not a feature of Behçet’s disease. This patient has an inferior branch retinal vein occlusion. Venous occlusion in the presence of posterior uveitis should always suggest the diagnosis of Behçet’s disease.

Fig. 10.44 This 33-year-old man presented with a history of oral ulcers and visual loss in his left eye with a mild posterior uveitis. The fluorescein angiogram shows a macular branch vein occlusion occurring along the vessel in the absence of an AV crossing indicating that the occlusion is vasculitic.

Fig. 10.45 White infiltrates of the inner retina sometimes associated with intraretinal haemorrhage can occur during the active phases of Behçet’s disease. Pathologically these are areas of neutrophils infiltrating the retina. In this patient the infiltrates resolved over a period of 2–3 weeks with treatment leaving the retinal pigment epithelium and retinal vasculature looking undisturbed.

Fig. 10.46 In the terminal phase there is optic atrophy secondary to destruction of the retina and its vasculature. The retinal arteries look like white threads from nonperfusion and gliosis. Although there is some disturbance at the macula, pigmentary changes are comparatively sparse for the severity of the disease.

By courtesy of Dr E M Graham.

Fig. 10.47 Major venous occlusions are seen elsewhere in Behçet’s disease. This patient has had an inferior vena cava thrombosis with a caput medusa due to venous bypass through the cutaneous veins of the abdominal wall.

Toxoplasmosis

Ocular toxoplasmosis is one of the commonest causes of posterior uveitis. Congenital ocular toxoplasmosis is acquired by transplacental infection of the fetus from a nonimmunized infected mother. The disease is extremely common in some parts of the world such as South America and West Africa and it seems that ocular involvement from acquired systemic disease in a nonimmunized patient is much more common than has been previously realized. The animal reservoir is in the cat and the organism has a predilection for neurological tissue. The parasite can persist encysted in the retina for many years. Retinal damage appears to be due to a combination of proliferating Toxoplasma organisms released from their cysts and directly invading the retinal cells, an inflammatory response, and possibly a secondary autoimmune reaction. IgM antibodies indicate recent infection; IgG antibodies indicate only previous infection and their level does not increase with relapsing retinal disease.

Toxoplasmosis is one of the few causes of uveitis that can be diagnosed by the fundal appearance; it does not cause anterior uveitis in the absence of fundal lesions which are pigmented, circumscribed scars usually in the posterior poles of one or both eyes. Visual acuity is lost if the macula or its axons are involved, but visual field defects can be caused by lesions elsewhere. The fundal lesions remain quiescent but have a tendency to reactivate in adults aged between 20 and 40 years producing a fluffy, white, chorioretinal lesion adjacent to previous chorioretinal scarring with posterior uveitis. If the lesion is small vitreous infiltration may be localized to this area. The activity of the lesions subsides over 3–4 months leaving further chorioretinal scarring. Many patients with mild reactivation of toxoplasmosis will settle without any treatment but if the macula or optic disc is threatened treatment with sulfonamides and pyrimethamine or clindamycin to destroy the organism, together with systemic steroids to suppress the inflammatory response, is usually given. No randomized controlled trial of such treatment has, however, shown benefit.

Fig. 10.48 Seroconversion during pregnancy carries a high risk of fetal damage, particularly in the first trimester, but it is exceptional for visual acuity to be lost in both eyes. Severe intracranial infection in a fetus can produce intracranial calcification, hydrocephalus, intellectual impairment and epilepsy.

Fig. 10.49 This is a typical quiescent Toxoplasma scar in the posterior pole. It is sharply circumscribed with retinal hyperpigmentation and pigment epithelial atrophy. Note the associated retinal nerve fibre defect.

Fig. 10.50 The fellow eye of the same patient as in Fig. 10.49 shows reactivation next to an area of previous scarring. A few weeks later the area of retinal necrosis with inflammatory infiltrate has become more discrete and the vitreous is clearing, leaving further retinal destruction and pigment atrophy. Note the associated posterior vitreous detachment.

Fig. 10.51 A particular feature of active toxoplasmic chorioretinitis is an arteritis of neighbouring vessels.

Fig. 10.52 Acquired toxoplasmosis is rare. A fresh circumscribed lesion is seen in the fundus with no evidence of previous scarring or pigmentation. The patient had a systemic febrile illness with lymphadenopathy. IgM antibodies to Toxoplasma were found in the blood.

Fig. 10.53 The pathology of toxoplasmosis is primarily retinal necrosis with secondary choroidal changes. After infection the organism remains encysted and intracellular in the retina as inactive bradyzoites (left) for many years. At some stage, for unknown reasons, the cyst ruptures to release the active tachyzoites (right). These proliferate to cause a necrotic retinitis before encysting again.

Left figure by courtesy of Mr C Pavesio.

Toxocariasis

The nematode Toxocara canis has its reservoir in dogs, especially young puppies; the ova persist for long periods in contaminated soil. Visceral larva migrans is the systemic form of acute toxocariasis. This occurs in older children and is associated with pulmonary infiltrates and transient eosinophilia; ocular involvement is comparatively uncommon. Ocular toxocariasis is typically seen in 2–4 year olds particularly if they have a tendency to eat dirt or have contact with puppies. The larvae migrate through the gut wall and can disseminate to the eye where they incite a granulomatous reaction. Toxocariasis occurs in two forms: a massive exudative white lesion containing the nematode in the posterior pole (sometimes presenting in a child as a poorly sighted eye with leucocoria) and a peripheral form with smaller white lesions in the equatorial retina with bands of retinal traction. There may be marked posterior uveitis. The disease is usually uniocular. Affected eyes are white and inflammatory signs are confined to the vitreous gel.

A positive serum enzyme-linked immunossorbent assay (ELISA) confirms previous infection by Toxocara; this may be negative with ocular disease and it may be necessary to repeat the test on aqueous or vitreous to confirm the diagnosis. In young children it is extremely important to distinguish toxocariasis from its main differential diagnosis, retinoblastoma. Apart from steroids to suppress the inflammatory response no other drug treatment is of proven benefit. It is possible, however, in some cases to remove the granuloma by vitreoretinal surgery and to clear the vitreous gel if there is chronic endophthalmitis.

Fig. 10.54 This is the fundus appearance of a 3-year-old child with a 6-month history of unilateral nonprogressive visual loss. A large white central granuloma has caused retinal traction. Visual acuity was counting fingers; the ELISA test was strongly positive and the family owned a puppy.

Fig. 10.55 Histological examination demonstrates a granuloma at the posterior pole of an infected eye. Serial sections and higher power demonstrate the encysted nematode.

Syphilis

Syphilis during pregnancy infects the fetus and produces a retinopathy. Active lesions are rarely seen in the neonate but are said to be focal, yellowish, spotty retinal pigment epithelial changes associated with vasculitis. This resolves to leave pigmentary scarring with areas of focal pigmentation and atrophy in the peripheral retina, the so-called ‘pepper and salt’ fundus which can sometimes be confused with retinitis pigmentosa. Following congenital syphilis, interstitial keratitis (see Ch. 6) may appear between the ages of 5 and 25 years. Patients may have other stigmata of infection such as nasal and dental deformities or nerve deafness. Progressive neurological deficit is, however, relatively uncommon.

Secondary syphilis, although rare, is becoming more common again and should be considered in any atypical intraocular inflammation, whether anterior or posterior, because of the serious consequences of missing the diagnosis. The absorption fluorescent treponemal antibody test (FTA Abs) is highly specific, and active infection can be distinguished from latent or treated infection by demonstrating IgM or IgG antibodies. The cerebrospinal fluid should be examined in all patients with ocular syphilis. Secondary syphilis is usually associated with a typical maculopapular rash on the limbs, trunk, hands and feet. Acute iritis may be present with iris papules known as roseola. More commonly chorioretinitis may be present with a mild posterior uveitis with focal, yellowish, subretinal infiltrates. The optic disc may be swollen and there may be serous retinal detachment. Patients who are HIV positive tend to show much more florid signs. Syphilitic retinopathy, if untreated, may resolve to leave a pigmentory retinopathy with arterial narrowing, optic disc pallor, and retinal pigment epithelial atrophy and scattered intraretinal pigmentation from RPE proliferation. Syphilitic chorio-retinopathy can usually be distinguished from true retinitis pigmentosa as visual fields and visual function are much better than would be expected with a retinal dystrophy.

Fig. 10.56 These photographs show the typical maculopapular rash on the hands from secondary syphilis. Spirochaetes can be found in the lesions by examining their exudate with dark field illumination.

Fig. 10.57 Patients with secondary syphilis usually have a mild posterior uveitis. Widespread yellowish subretinal infiltrates are a common feature and can suggest the diagnosis. This patient was also HIV and hepatitis B positive.

Fig. 10.58 This patient was known to have had congenital syphilis. The optic disc is pale, retinal vessels are attenuated and there is widespread chorioretinal atrophy. The equatorial retina shows large clumps of intraretinal pigmentation. Patients often have good visual function despite their retinopathy. Visual loss is usually due to keratitis and subsequent cataract formation.

Ocular tuberculosis

Ocular tuberculosis is rare but should always be considered in patients with atypical anterior uveitis, retinal vasculitis or choroidal infiltrates, particularly in the presence of HIV. Patients usually have a florid positive tuberculin (Mantoux Heat Test). Patients require chest radiographs and culture of sputum and urine for tuberculi bacilli. Systemic evidence of active tuberculosis can be difficult to substantiate. Circumstantial proof of the diagnosis is often demonstrated by rapid improvement in the ocular signs with a short course of antituberculous chemotherapy. Systemic steroids may be required for control of the ocular inflammation but if there is a possibility of tuberculosis appropriate chemotherapy must be given to prevent disseminated systemic disease. Eales’ disease (retinal vasculitis, peripheral vascular closure and neo-vascularization with a strange propensity to affect the left eye) is particularly common in the Indian subcontinent and is thought to be associated with a hypersensitivity response to tuberculin.

Fig. 10.59 This Pakistani woman had a chronic anterior uveitis with marked nodular involvement of the iris, unresponsive to topical steroid treatment. Chest radiography showed old tuberculous changes and the patient had a strongly positive Mantoux reaction although sputum culture was negative. The iris appearance improved dramatically after 2 weeks of antituberculous chemotherapy.

Fig. 10.60 This patient had miliary tuberculosis; a single choroidal tubercule can be seen as a creamy, diffuse, subretinal swelling. Nonspecific pigment epithelial scarring remains after appropriate chemotherapy. Choroidal tubercles are frequently bilateral and multifocal.

Fig. 10.61 Florid retinal vasculitis can be associated with tuberculosis, especially in Asiatic patients. Posterior uveitis is relatively mild but retinal vasculitis is marked and there is vascular closure and haemorrhage which frequently progresses to neovascularization. The fluorescein angiogram showed peripheral closure with early new vessels and patchy leakage.

Acute retinal necrosis

Patients present with vitreous cellular infiltrate and characteristic patchy, fluffy white areas in the peripheral fundus that become confluent areas of whitish retinal necrosis, associated with occlusive arteritis and granulomatous anterior uveitis that progress to increasing retinal destruction and detachment if untreated. Both eyes are ultimately involved in 20–80 per cent of patients. The disease is caused by herpes simplex or zoster. The retinal changes are similar with each virus, but patients with simplex infection tend to be younger (less than 40 years) in comparison to those with zoster (above 50 years). Acute retinal necrosis may sometimes follow a recent herpes simplex cutaneous eruption or encephalitis. It can occur in either entirely healthy or immunosuppressed patients. It is important to identify the causative virus by polymerase chain reaction (PCR) on a vitreous biopsy to target specific antiviral therapy. Treatment with intravenous antivirals for 10 days followed by oral therapy for 3 months usually halts the disease and prevents relapse or progression into the other eye. Patients with HIV may relapse with cessation of treatment. Following successful treatment, retinal detachment with giant tears occurring along the demarcation line between normal and affected retina happens in up to 75 per cent of patients 4–8 weeks after the onset of retinitis; prophylactic treatment to prevent this with vitrectomy and endo-laser remains controversial.

Fig. 10.62 Acute retinal necrosis. This otherwise fit 56-year-old man presented with blurred vision in his left eye of 5 days’ duration. The fundal view is very hazy because of the vitreous infiltrate but patchy white retinal infiltrates can be discerned nasal to the disc.

Fig. 10.63 Vitreous biopsy was positive for herpes zoster on PCR. After 5 days of intravenous antiviral treatment the retinal appearances are clearing and the infiltrates can be seen more clearly.

Fig. 10.64 Three months later the patient suffered a retinal detachment that was treated with silicone oil and endo-laser, leaving HM vision. Note the optic atrophy and marked vascular closure.

Fig. 10.65 This patient shows an arteritis coexistent with peripheral acute necrosis. Optic disc and optic nerve arteritis are common in acute retinal necrosis and may contribute to the visual loss. The patient had a positive PCR for herpes zoster.

Acquired immune deficiency syndrome (AIDS)

HIV-associated diseases should be considered in any patient with uveitis with social risk factors, from a high prevalence area or with unusual or atypical uveitis. Both Kaposi’s sarcoma (see Ch. 3) and herpes zoster (see Ch. 4) can affect the anterior segment. Idiopathic cotton wool spots may be seen in a number of cases as transient lesions that disappear spontaneously within 6–8 weeks. The commonest form of retinal infection is cytomegalovirus retinitis although this has become less common with the success of highly active antiretroviral (HAART) therapy. Cyto-megalovirus retinitis is associated with CD4 counts of less than 50 and is uncommon if the count is over 100. Untreated the retinopathy progresses slowly. Both eyes become involved and the lesions relentlessly increase in area with the central part of the lesion becoming atrophic. The retina is destroyed within 6 months. Retinal detachment is common.

A wide variety of other opportunistic infections occur less commonly including toxoplasmosis, herpes simplex or zoster retinitis, cryptococcosis, atypical mycobacteria and Pneumocystis carinii. Secondary syphilis is well recognized and produces a more florid uveitis than in otherwise normal individuals. Intraocular lymphoma must also be considered.

Immune recovery uveitis is seen in patients who have had cytomegalovirus retinitis that has been treated and become quiescent on maintenance therapy. As their CD4 count rises to above 100 with HAART therapy these patients develop a low-grade intermediate type of uveitis with cystoid macular oedema.

Fig. 10.66 HIV retinopathy is the most common form of ocular involvement in patients with AIDS and is seen in more than 50 per cent of patients prior to HAART. Cottonwool spots are seen in the posterior pole; they are asymptomatic and resolve over 4–6 weeks. They are thought to be caused by HIV infection of retinal vascular endothelium causing microinfarction.

Fig. 10.67 This 46-year-old man presented with poor vision in his left eye. Examination showed a macular lesion with a peripheral lesion typical of cytomegalovirus retinitis. There are creamy areas of retinal necrosis and haemorrhage alongside retinal vessels with a minimal vitreous cellular infiltrate.

Fig. 10.68 The patient was treated with ganciclovir and the lesions improved, but relapsed 3 months later when he discontinued treatment. This led to further retinal destruction and involvement of the fellow eye.

Fig. 10.69 The patient responded to another course of ganciclovir and continued to take maintenance therapy. At this stage the fundi are quiescent with areas of retinal atrophy, pallor of the optic discs and vascular attenuation.

Fig. 10.70 Pathological examination of the same patient shows areas of complete retinal destruction with a sparse inflammatory cellular infiltrate and the typical ‘owl’s eye’ intracellular inclusions of cytomegalovirus.

Fig. 10.71 Progressive outer retinal necrosis (PORN) is a multifocal form of herpes zoster retinitis seen in patients with AIDS with very low CD4 counts. It is usually bilateral with minimal signs of ocular inflammation. The deep retinal lesions rapidly become confluent with total visual loss.

By courtesy of Dr P McCluskey.

Fig. 10.72 Choroidal pneumocystis is characterized by multiple subretinal plaques 1–3 disc diameters in size in the posterior pole. The lesions slowly enlarge in the absence of inflammation. Vision is usually good. The ocular lesions are an early sign of life-threatening systemic infection.

By courtesy of Dr E M Graham.

Subacute sclerosing panencephalitis

This rare condition is due to persistent measles infection in the brain. It affects children aged 6–14 years and is fatal from progressive neurological degeneration over 1–2 years. Patients present with myoclonic jerks and intellectual impairment. The EEG and cerebrospinal fluid (CSF) changes are diagnostic.

Fig. 10.73 There is a mild posterior uveitis with retinal infiltrates later progressing to pigmentary atrophy.