Ординатура / Офтальмология / Английские материалы / Clinical Ophthalmology A Systematic Approach 7th Edition_Kanski, Bowling_2011

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Miscellaneous parasitic uveitis

Onchocerciasis

Pathogenesis

Onchocerciasis or river blindness is caused by infestation with the parasitic helminth Onchocerca volvulus. The normal vector is the black fly Simulium spp., an obligate intermediate host, which breeds in fast flowing water. Larvae are transmitted when the fly bites to obtain blood, which then mature into adult worms that produce millions of microfilariae over years (Fig. 11.31). Wolbachia (a rickettsia) lives symbiotically in the coat of the microfilaria in a fashion similar to mitochondria and are important for fertility of the female filarial worm. Onchocerciasis is endemic in West, Central and East Africa, with small foci in central and South America, Sudan and Yemen. Infecting nearly 18 million people most of whom are asymptomatic but with an estimated 270 000 blind and half a million visually impaired. The disease is especially severe in savannah areas.

Fig. 11.31 Life cycle of Onchocerca volvulus

Systemic features

1Signs

•The most common early manifestation is pruritus which is followed by a maculopapular rash often involving the buttocks and extremities (Fig. 11.32A).

•Chronic lesions are characterized by focal areas of hypoand hyperpigmentation on the shins (‘leopard’ skin – Fig. 11.32B).

•With time the skin may become thickened and wrinkled as a result of constant scratching (‘lizard’ skin – Fig. 11.32C).

•Subcutaneous nodules (onchocercomas) consisting of encapsulated worms develop nodules over bony prominences (Fig. 11.32D) and the head.

•Occasionally the lymph nodes become grossly enlarged resulting in chronic lymphatic obstruction and lymphoedema.

2Treatment is with ivermectin given as an annual single dose. Although it acts rapidly to reduce the number of skin microfilariae it depletes them for only a few months after which they reappear at levels of 20% or more of pre-treatment numbers within 1 year, which is sufficient for transmission to continue. Therapies targeting Wolbachia show great promise, including a 6-week course of doxycycline.

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Fig. 11.32 Onchocerciasis. (A) Maculopapular rash; (B) ‘leopard’ skin; (C) ‘lizard’ skin; (D) subcutaneous nodule (onchocercoma)

(Courtesy of C Gilbert)

Ocular features

1Anterior segment involvement includes sclerosing keratitis and anterior uveitis that may result in pear-shaped pupillary dilatation. Live floating microfilariae may be seen after the patient has bent face down for a few minutes and then immediately been examined on the slit-lamp.

2Chorioretinitis is usually bilateral and predominantly involves the posterior fundus. The severity varies from atrophy and clumping of the RPE which may resemble choroidal ‘sclerosis’ (Fig. 11.33A) to widespread chorioretinal atrophy (Fig. 11.33B).

3Treatment is aimed at eradicating the source of the microfilariae with ivermectin. Anterior uveitis responds to steroids but the chorioretinal lesions are irreversible.

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Fig. 11.33 Ocular onchocerciasis. (A) Choroidal ‘sclerosis’ and pigmentary changes; (B) severe chorioretinal atrophy

Cysticercosis

1Pathogenesis. Cysticercosis refers to a parasitic infestation by Cysticercus cellulosae, the larval form of the pork tapeworm Taenia solium. Pigs are the intermediate hosts and humans are the definitive hosts, acquiring the disease by ingesting cysts of T. solium from contaminated pork, vegetables or water.

2Systemic disease often involves the lungs, muscles and brain.

3 Investigations involve radiology of the chest (Fig. 11.34) and muscles to detect calcified cysts.

4Ocular features

•Cysts involving conjunctiva, and occasionally the orbit and eyelids.

•The anterior chamber may show a free-floating cyst (Fig. 11.35A).

•The larvae may enter the subretinal space and cause retinal detachment (Fig. 11.35B).

•The larvae can also pass into the vitreous where released toxins incite an intense inflammatory reaction which may ultimately lead to blindness.

5Treatment involves systemic steroids to control inflammation together with surgical removal of the larvae from the anterior chamber, vitreous or subretinal space.

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Fig. 11.34 Chest radiograph shows calcified cysticercus cysts

(Courtesy of CA Hart and P Shears, from Color Atlas of Medical Microbiology, Mosby 2004)

Fig. 11.35 Ocular cysticercosis. (A) Anterior chamber cyst; (B) subretinal cyst with overlying retinal detachment

(Courtesy of A Pearson)

Diffuse unilateral subacute neuroretinitis

1Pathogenesis. Diffuse unilateral subacute neuroretinitis (DUSN) is characterized by a motile subretinal nematode that typically causes monocular visual loss in an otherwise healthy individual. Baylisascaris procyonis, the raccoon roundworm, as well as Ancylostoma caninum, the dog hookworm, has been implicated but it is possible that different worms are capable of producing the same clinical picture.

2Presentation is with insidious loss of peripheral and central vision that may be associated with transient visual obscurations.

3Signs

•Crops of evanescent grey-white outer retinal lesions that tend to resolve within 10 days (Fig. 11.36A) whilst fresh crops appear.

•Papillitis, retinal vasculitis and mild vitritis.

•Optic atrophy, retinal vascular attenuation and diffuse RPE degeneration in end-stage disease (Fig. 11.36B).

•Subretinal scarring.

4ERG is subnormal, even in early disease.

5Treatment involves direct laser photocoagulation of the subretinal nematode by first surrounding it with a ring of burns, which restrict its movement, and then applying heavy burns to the entire area. Systemic albendazole may also be beneficial.

6 Differential diagnosis includes papillitis and multiple evanescent white dot syndrome.

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Fig. 11.36 Diffuse unilateral subacute neuroretinitis. (A) Active lesions; (B) optic atrophy, vascular attenuation and diffuse RPEdegeneration

(Courtesy of J Donald M Gass, from Stereoscopic Atlas of Macular Diseases, Mosby 1997 – fig. A; C de A Garcia – fig. B).

Choroidal pneumocystosis

1Pathogenesis. Pneumocystis jirovecii, a fungus, is a major cause of morbidity and mortality in AIDS. The presence of choroidal involvement can be an important sign of extrapulmonary systemic dissemination. Most patients with choroiditis have received inhaled pentamidine as prophylaxis against pneumocystis pneumonia. In contrast with systemic prophylaxis this protects only the lungs, allowing the organisms to disseminate throughout the body.

2Signs

•Flat, yellow, round, choroidal lesions, scattered throughout the posterior pole, which are frequently bilateral and not associated with vitritis (Fig. 11.37A).

•The lesions may coalesce and produce large geographic patches (Fig. 11.37B).

•Even when the fovea is involved there is little visual impairment.

3 Treatment involves intravenous trimethoprim and sulfamethoxazole, or parenteral pentamidine.

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Fig. 11.37 Choroidal pneumocystosis. (A) Multifocal choroidal lesions; (B) large coalescent lesion

(Courtesy of S Mitchell – fig. A)

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Uveitis in acquired immunodeficiency syndrome

Introduction

Pathogenesis

Acquired immunodeficiency syndrome (AIDS) is caused by the human immunodeficiency virus (HIV). On a worldwide basis, heterosexual intercourse is the predominant mode of transmission; in the western world, however, AIDS is commonly transmitted by male homosexual contact. Transmission may also occur by contaminated blood or needles, transplacentally or via breast milk. HIV targets CD4+ T cells, which are vital to the initiation of the immune response to pathogens. A steady decline in the absolute number of CD4+ T cells therefore occurs, resulting in progressive immune deficiency, particularly of cell mediated immunity. Regular estimation of the CD4+ T cell count is therefore a useful measure of disease progression.

Systemic features

1Progression of HIV infection

aAcute seroconversion illness. HIV infection is sometimes followed a few weeks later by constitutional symptoms such as fever, headache, malaise, and a maculopapular rash associated with generalized lymphadenopathy, soon after which antiHIV antibodies appear.

bAn asymptomatic phase, often lasting many years follows, during which there is a steady depletion of CD4+ T cells.

cSymptomatic HIV infection (AIDS) then follows, characterized by immunosuppression with opportunistic infections, neoplasms and tissue damage directly due to HIV infection.

2Opportunistic infections with protozoa (e.g. Toxoplasma gandii and Cryptosporidium spp.), viruses (e.g. CMV, HSV) fungi (e.g.

Pneumocystis jirovecii (Fig. 11.38A), Cryptococcus neoformans and Candida albicans (Fig. 11.38B), and bacteria (e.g. M. aviumintracellulare and Bartonella henselae).

3Tumours include Kaposi sarcoma (Fig. 11.38C), non-Hodgkin B-cell lymphoma and squamous cell carcinoma of the conjunctiva (in Africa), cervix and anus.

4Other manifestations include HIV wasting syndrome (Fig. 11.38D), HIV encephalopathy and progressive multifocal leucoencephalopathy.

Fig. 11.38 Acquired immunodeficiency syndrome. (A) Pneumocystis pneumonia; (B) oral candidiasis; (C) Kaposi sarcoma; (D) HIV wasting syndrome

Serology

•Serological testing for HIV infection should be performed only with informed consent after proper counselling, due to the profound implications of a positive result. HIV is confirmed most commonly by the demonstration of anti-HIV antibodies in the serum, by using the ELISA and Western blot tests.

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•‘Seroconversion’ may take 3 months or longer to occur following exposure to the virus, sometimes necessitating serial testing in individuals at high risk.

•Subsequent to the establishment of HIV positivity, CD4+ T cell counts are measured every 3 months. A count <200/mm3 implies a high risk of HIV related disease; AIDS is diagnosed when an HIV positive subject develops one or more of a defined list of indicator diseases and/or this CD4+ cell level.

Treatment

Although there is no cure for AIDS, the progression of disease can be radically slowed by a number of drugs. The aim of treatment is to reduce the plasma viral load. Ideally therapy should be commenced before the development of irreversible damage to the immune system.

1Indications for commencement of anti-HIV therapy include:

•Symptomatic HIV disease.

•CD4+ T lymphocyte count <300/mm3.

•Rapidly falling CD4+ T lymphocyte count.

•Viral load >10 000/mL of plasma.

2Drug treatment is with ‘highly active antiretroviral therapy’ (HAART), which involves 2 nucleoside reverse transcriptase inhibitors with either a non-nucleoside reverse transcriptase inhibitor or 1 or 2 protease inhibitors.

aNucleoside reverse transcriptase inhibitors include zidovudine, lamivudine and zalcitabine.

b Protease inhibitors include amprenavir, indinavir and neltinavir.

cNon-nucleoside reverse transcriptase inhibitors include efavirenz and nevirapine.

Ocular features

1 Eyelid. Blepharitis, Kaposi sarcoma, multiple molluscum lesions and herpes zoster ophthalmicus. 2 Orbital. Cellulitis, usually from contiguous sinus infection, and B-cell lymphoma.

3Anterior segment

•Conjunctival Kaposi sarcoma, squamous cell carcinoma and microangiopathy.

•Keratitis due to microsporidia, herpes simplex and herpes zoster.

•Keratoconjunctivitis sicca.

•Anterior uveitis (usually secondary to systemic drug toxicity: rifabutin, cidofovir).

4Posterior segment

•HIV microangiopathy (see below).

•HlV retinitis (see below).

•Cytomegalovirus retinitis (see below).

•Progressive outer retinal necrosis (see below).

•Choroidal pneumocystosis (see parasitic uveitis).

•Toxoplasmosis, frequently atypical.

•Choroidal cryptococcosis.

•B-cell intraocular lymphoma.

HIV microangiopathy

Retinal microangiopathy is the most frequent retinopathy in patients with AIDS, developing in up to 70% of patients and is associated with a declining CD4+ count. Postulated causes include immune complex deposition, HIV infection of the retinal vascular endothelium, haemorheological abnormalities and abnormal retinal haemodynamics.

1Signs. Cotton wool spots which may be associated with retinal haemorrhages and capillary abnormalities (Fig. 11.39).

2Differential diagnosis. The lesions may be mistaken for early CMV retinitis. However, in contrast to CMV, lesions are usually asymptomatic and almost invariably disappear spontaneously after several weeks.

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Fig. 11.39 HIV microangiopathy

Cytomegalovirus retinitis

Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection among patients with AIDS. Since the advent of HAART its incidence has declined and its rate of progression reduced, even in patients with low CD4+ T cell counts. It also appears that the rates of second eye involvement and retinal detachment are less than in the pre-HAART era.

Clinical features

1Indolent retinitis frequently starts in the periphery and progresses slowly. It is characterized by a mild granular opacification which may be associated with a few punctate haemorrhages, but vasculitis is absent (Fig. 11.40A).

2Fulminating retinitis.

•Mild vitritis.

•Vasculitis with perivascular sheathing and retinal opacification.

•Dense, white, well-demarcated, geographical areas of confluent opacification often associated with retinal haemorrhages (Fig. 11.40B).

•Slow but relentless ‘brushfire-like’ extension along the course of the retinal vascular arcades that may involve the optic nerve head (Fig. 11.40C).

•Retinal detachment associated with large posterior breaks may occur in uncontrolled disease (Fig. 11.40D) and require vitreoretinal surgery and the use of silicone oil tamponade.

Fig. 11.40 Cytomegalovirus retinitis. (A) Indolent retinitis; (B) fulminating disease; (C) advanced disease involving the optic nerve head; (D) large posterior retinal tear with shallow localized detachment

(Courtesy of C Barry – fig. D)

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Systemic treatment

1Valganciclovir is a pro-drug of ganciclovir that has better gastrointestinal absorption and is as effective as intravenous ganciclovir itself for treatment and prophylaxis. The induction dose is 900 mg b.d. and the daily maintenance dose is 900 mg.

2Ganciclovir is initially given intravenously (induction) 5 mg/kg every 12 hours for 2–3 weeks, then every 24 hours. Ganciclovir is effective in 80% of patients but 50% subsequently relapse and require reinduction of therapy. The drug carries a high risk of bone marrow suppression which often forces interruption of treatment.

3Intravenous foscarnet. The initial dose is 60 mg/kg every 8 hours for 2–3 weeks and then 90–120 mg every 24 hours. Side-effects include nephrotoxicity, electrolyte disturbances and seizures. Foscarnet can also be given intravitreally (2.4 mg in 0.1 mL).

4Intravenous cidofovir, 5 mg/kg once weekly for 2 weeks and then every 2 weeks may be used where other agents are unsuitable. It must be administered in combination with probenecid. Side-effects include nephrotoxicity, neutropenia and anterior uveitis.

Intravitreal treatment

1Ganciclovir slow-release device (Vitrasert®) is as effective as intravenous therapy (Fig. 11.41A). The duration of efficacy is 8 months, which is superior to intravenous therapy with either ganciclovir or foscarnet (average 60 days). However, it does not prevent involvement of the fellow eye. Complications include cataract, vitreous haemorrhage, retinal detachment and endophthalmitis.

2Injection

aGanciclovir (2.0–2.5 mg in 0.1 mL) may be performed prior to implantation of a slow-release implant to determine the likely response to the drug.

bFomivirsen has a different mechanism of action from other agents. Adverse effects include anterior uveitis, vitritis, cataract and rarely retinopathy.

cCidofovir (15–20 µg in 0.1 mL) may occasionally cause severe inflammation leading to hypotony and even phthisis bulbi.

Fig. 11.41 Treatment of cytomegalovirus retinitis. (A) Slow-release implant containing ganciclovir that has caused localized lens opacity; (B) regressing retinitis after treatment

(Courtesy of S Milewski – fig. A; L Merin – fig. B)

Prognosis

Initially 95% of cases respond to treatment. Regression is characterized by fewer haemorrhages and less opacification, followed by diffuse atrophy and mild pigmentary changes (Fig. 11.41B). Since the introduction of HAART therapy the incidence of CNV retinitis has decreased and many patients have had their treatment of retinitis stopped after immune recovery (CD4 > 100–150). Many patients with HAART-induced

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