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16  Infectious Diseases of the Pediatric Retina

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smear taken from the aqueous or the vitreous. Diagnosis can only be confirmed by positive culture of the organism from a diagnostic specimen, a procedure fraught with difficulties. Polymerase chain reaction (PCR), which is used to detect a specific segments of the bacteria’s DNA, has recently been used in diagnosis [360]. PCR appears to be particularly useful for diagnosing primary ocular tuberculosis.

16.5.2.3  Tuberculosis and AIDS

Patients with AIDS have almost 500 times the incidence of tuberculosis than the general population [361]. M. tuberculosis is more pathogenic than other pathogens associated with HIV, and this may account for the fact that tuberculosis can occur in patients who are HIV positive but who do not have AIDS. There are several reports of intraocular involvement in HIV patients, mostly in the form of choroidal granulomas or choroidal nodules [360, 362–364]. Unfortunately, diagnosis of tuberculosis in HIV patients is not easy because the clinical and radiological features are not typical and may resemble other associated infections with HIV [365, 366].

16.5.2.4  Treatment

Systemic therapy should always be given as the primary treatment for ocular tuberculosis because pulmonary or other foci of usually coexist. First line treatment agents include izoniazid, rifampin, pyrazinamide, ethambutol, and streptomycin. Patients who develop resistance to first line drugs can use any of the second line drugs that include kanamycin, amikacin, capreomycin, ethionamide, cycloserine, P-aminosalicylic acid (PAS), and quinoline. Multidrug regimens are recommended. The guideline for treatment by the American Thoracic Society consists of a 2-month initial phase with izoniazid, rifampin, and pyrazinamide followed by a 4-month continuation phase of izoniazid andrifampinforatotalof6month[367].Corticosteroids are sometimes used cautiously in conjunction with antimicrobial therapy. Bacteriological evaluation is the preferred method of monitoring the response to treatment for systemic disease, while monitoring treatment response of ocular disease is done primarily on a clinical basis.

16.6  Rare Childhood Bacterial Diseases

16.6.1  Brucellosis

Brucella is a rare cause of uveitis seen most commonly in developing countries. It is caused by gram-negative brucella melitensis or brucella abortus and is transmitted to man through ingestion of unpasteurized milk or milk products [368] or by airborne spread [369].

Ocular manifestations can occur in the acute or the chronic stage of the disease. Anterior segment manifestations include either granulomatous or nongranulomatous uveitis with the possibility of chronic sequelae of uveitis such as posterior synechiae formation and the development of complicated cataract. Posterior segment manifestations are variable and include vitritis, vasculitis, and retinitis. Papillitis is a possible complication, and vision loss has occasionally been attributed to optic nerve damage [370].

Diagnosis of brucellosis may be difficult owing to the nonspecific systemic manifestations and similarity of the clinical picture to other infectious diseases. Systemic manifestations include malaise, loss of weight, lymphadenopathy, hepatosplenomegaly, and elevated liver enzymes [371, 372]. If the diagnosis is not made or if proper treatment is not given, the disease enters the chronic stage with a wide variety of manifestations including a rheumatic-like disease, cardiovascular and neurological manifestation. Diagnosis of ocular brucellosis is mainly through isolation of the organism by culture of ocular fluid or by measuring the Witmer’s relation between the serous and ocular specific antibodies [373]. If cultures prove negative and the diagnosis is still suspected, serological tests may be used to achieve a presumptive diagnosis.

Treatment of ocular brucellosis includes oral rifampicin and doxycycline with or without streptomycin intramuscularly. Third generation cephalosporines as ceftriaxone and ceftizoxime are also effective [374]. Adjunctive corticosteroids can be used to prevent ocular reaction.

16.6.2  Leptospirosis

Leptospirosis is one of the most common zoonoses in the world. The causative agent is a gram-negative spirochete leptospira [375]. The clinical manifestations

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vary from a mild illness with fever, myalgia, and headache to a severe Weil’s syndrome with liver dysfunction, microvascular hemorrhage, and renal failure.

Subconjunctival hemorrhage is the most common ocular complication of leptospirosis [376, 377]. Leptospira uveitis appears to be clinically distinct from other uveitic entities. Traditionally, leptospira uveitis is divided into two main categories: [1] self-limiting anterior uveitis [377] and [2] posterior segment involvement with cotton-wool spots, choroiditis, retinal hemorrhage, vitreous membrane, and papillitis [378]. Retinal vasculitis has also been reported [379]. Bilateral panuveitis, papillitis, and lack of visual deficit are characteristic of leptospiral infection and can be used as a diagnostic algorithm in leptospira endemic areas where confirmatory serology and PCR are often not available. Antimicrobial agents, if used for treatment, should be administered early in the course of the disease. Generally, leptospirosis is a self-limited disease with a favorable prognosis. Even in patients with severe icteric leptospirosis, recovery may take place without specific treatment.

16.6.3  Lyme Disease

Lyme borreliosis is a tick-borne infection caused by the spirochaete borrelia burgdorferi .It is becoming increasing prevalent in many countries due to spread of the organism or perhaps due to increased recognition of the disease. Despite the fact that systemic manifestations of lyme are prominent, ocular findings are rare and less prominent [380].

Systemic manifestations include erythema migrans, neurological manifestations with involvement of the meninges and/or cranial nerves, and cardiovascular disease [381]. The most frequent systemic manifestation of late disease is lyme arthritis.

Ocular involvement occurs usually in the course of neuroborreliosis [382], and manifestations are similar in adults and children. Anterior segment manifestations include transient conjunctivitis and keratitis [383]. Anterior uveitis, which is the most frequent intraocular inflammatory disease, is rarely seen in children [384]. Lyme borreliosis has been described as a cause of intermediate uveitis with vitritis, though [385] intermediate uveitis is rarely seen in children [386, 387]. Posterior segment manifestations include choroiditis, vitritis

[388], neuroretinitis, and optic neuritis. Retinal vasculitis has also been reported [389].

Ocular lyme borreliosis can typically be diagnosed in the early stages on the basis of medical history, clinical findings, and serological tests including ELIZA and western blot analysis [389]. In the late phases of the disease however, ocular borreliosis may be underdiagnosed because of weak seropositivity or seronegativity in ELIZA assays [389]. Early localized lyme disease may be treated with oxycyclin in children above 8 years of age or amoxicillin for younger children. More advanced or persistent disease is best treated with IV ceftriaxone [390]. Antibiotics administration early in the course of the disease has a better prognosis than therapy initiated at later stages.

16.6.4  Cat Scratch Disease

Cat scratch disease is a self-limiting systemic disease, which is caused by the gram-negative bacillus, bartonella hensella. The disease can be transmitted by the bite or the scratch of an infected animal, often a young cat or a kitten [391]. Other animals, such as dogs, may also harbor the agent. It has been suggested that cat fleas might play a role as an arthropod vector [392].

The most common systemic finding is lymphadenopathy and constitutional symptoms with malaise, fatigue, and fever. Other manifestations include respiratory problems, neurological manifestations, and involvement of the liver or the spleen [391, 393, 394].

Reported ocular manifestations of cat scratch fever include neuroretinitis (optic disc edema with macular star formation), optic neuritis, focal chorioretinitis, serous retinal detachment, and vitritis [395–399]. A vasculopathic effect of bartonella infection has been reported, including retinal vein or artery occlusion [400]. Although optic disc edema and stellate maculopathy are the most characteristic posterior segment manifestations, the most common finding is the presence of retinal or chorioretinal white inflammatory foci, which may leave atrophic scars in the retinal pigment epithelium after resolution [400–402].

A variety of laboratory tests including lymph node biopsy, skin test antigen, and an ELIZA test are available to help diagnose cat scratch fever. The use of antibiotics for treatment vs. conservative symptomatic treatment is still debatable. Adjunctive corticosteroids therapy has