Hospital for Sick Children's, The: Atlas of Pediatric Ophthalmology & Strabismus, 1st Edition

Ocular Manifestations of Systemic Disease


Infectious Diseases

Alex V. Levin

Thomas W. Wilson

Nasrin Najm-Tehrani

Virtually every infectious disease may affect the eye either through direct infection, hematogenous spread, contiguous spread, or complications related to a primary infection at another site. This chapter focuses on ocular complications of systemic and remote infection. Diagnosis of the ocular manifestation might require culture from a site remote from the eye or, less commonly, sampling of intraocular fluids or tissues. Given the difficulty in obtaining intraocular tissues for culture, careful attention to remote sites for diagnostic culture or titers becomes essential.

Suspicion of an infectious cause for an ocular abnormality might stem from the presence of systemic signs such as fever, shock, or other more localized indicators. The presence of infection in the cerebrospinal fluid or blood is particularly worrisome with regard to potential ocular involvement. Transplacental spread of infection to a fetus may present with multiorgan system involvement or even malformations. Taking a careful history is another powerful diagnostic tool and should include queries regarding contacts and exposures, course of the illness, other systemic indicators of infection, treatment with antibiotics or other agents, contact with pets and other animals, travel, and, in the case of suspected fetal infection, pregnancy history. Diagnostic studies on family members (e.g., the mother in a case of suspected fetal infection) may be appropriate in some circumstances.

Some ocular complications of systemic and remote infectious disease are treated by topical or intraocular agents, whereas others require systemic treatment. When diagnostic tissue culture is not obtainable, broad-spectrum antibiotic coverage may be appropriate. The American Academy of Pediatrics Red Book is a particularly useful reference for diagnosis and treatment guidelines.



Figure 19.1 Gradenigo Syndrome

Aggressive bacterial otitis media can lead to involvement of the petrous bone and mastoid. Cranial nerve VI runs over the intracranial petrous bone on its way to the ipsilateral lateral rectus muscle. Inflammation in the intracranial space can result in an abduction deficit, as shown in this child's right eye (Chapter 1: Strabismus, Fig. 1.51). Other diagnostic findings include otitis media, papilledema from increased intracranial pressure, signs of systemic illness (in particular pain, fever, and headache), and diagnostic inflammatory signs in the region of the petrous bone with or without mastoiditis on computed tomography scan or magnetic resonance imaging.


Figure 19.2 Necrotizing Fasciitis/ Flesh-eating Disease

Necrotizing fasciitis is a cutaneous disease with aggressive destruction of the skin and underlying tissues. Skin injury almost always precedes the infection. Death can result within days. The infection is caused by anaerobic bacteria with or without aerobic bacteria or group A streptococcus (as shown in the photograph). Pain and fever are key signs, along with a characteristic feathery appearance to the infected area with air on computed tomography or magnetic resonance imaging. Debridement and a variety of antibiotics have been the cornerstone of treatment. Hyperbaric oxygen therapy has also been used. Survivors usually require extensive reconstructive plastic surgery.


Figure 19.3 Toxoplasmosis

Toxoplasmosis is an infectious disease caused by the protozoan Toxoplasma gondii. Humans acquire the infection from ingestion of oocysts contained within cat feces or undercooked meat. Congenital toxoplasmosis occurs following transplacental transmission of the protozoan and presents with the classic triad of chorioretinitis, hydrocephalus, and intracranial calcification. This photograph shows optic atrophy and a typical dense chorioretinal scar, typically located in the macula. Diagnosis of toxoplasmosis can be confirmed by serology tests. Treatment modalities include pyrimethamine and sulfadiazine.




Figure 19.4 Congenital Rubella

Clinical findings of congenital rubella include posterior cervical and retroauricular adenopathy, a rash on the soft palate and pharyngeal mucosa, growth and mental retardation, congenital heart defects (especially peripheral pulmonic stenosis), hearing loss, hepatosplenomegaly, intracranial calcification, and thrombocytopenic purpura. Ocular manifestations include cataracts, glaucoma, microphthalmia, and corneal endotheliitis. Active virus can be isolated from the lens for diagnosis. Retinal pigmentary disturbances include a “salt and pepper” mottling due to internal limiting membrane gliosis and retinal pigment epithelium hyperplasia. The vision tends to be normal with a normal electroretinogram, which differentiates this condition from other retinal dystrophies. Retinal blood vessels and the optic nerve may appear surprisingly healthy.


Figure 19.5 Herpes Simplex

Herpes simplex virus type I (and less commonly type II) primary infection typically occurs within the first decade following contact with an adult with oral herpes and presents with aphthous stomatitis, dermatitis, or conjunctivitis. The herpes simplex virus becomes latent within the trigeminal ganglion. Factors that may cause recurrence include stress, ultraviolet radiation, menses, fever, and trauma. The skin lesions typically clear within 1 to 2 weeks without significant scarring, although they may become secondarily infected with bacteria and cause a preseptal cellulitis. Approximately 25% of patients with primary herpetic conjunctivitis will develop keratitis including superficial punctate keratitis, subepithelial infiltrates, and possibly dendrites. Patients with primary herpetic conjunctivitis should be treated with topical antiviral ointment or drops.


Figure 19.6 Corneal Herpes

Recurrent herpes simplex is caused by latency of the herpes virus within the trigeminal ganglion. Clinical manifestations include vesicular lesions on the lids, conjunctivitis, epithelial keratitis (classically in the form of dendrites with terminal bulbs), stromal keratitis, sclerokeratitis, and endotheliitis. Blepharoconjunctivitis rarely occurs without corneal involvement. The dendrites will spontaneously heal over 1 to 2 weeks and may be associated with loss of corneal sensation. Severe infections can cause stromal scarring (shown here) and vascularization. Patients should be treated with antiviral medications, including trifluorothymidine drops nine times a day. Patients may also benefit from debridement of the corneal epithelium.




Figure 19.7 Varicella Zoster

Herpes zoster ophthalmicus involves the ophthalmic branch of the trigeminal nerve and is secondary to reactivation of the varicella virus within the trigeminal ganglion. The reactivation is more common in the elderly population and in the immunocompromised host. Postherpetic neuralgia (severe pain and pruritus) can cause patients to excoriate themselves (right image). Other ocular complications of herpes zoster include uveitis, retinal vasculitis, acute retinal necrosis, cranial nerve palsies, and neuroretinitis. Treatment of zoster includes steroids to control the ocular inflammation as well as systemic antiviral medications, including acyclovir, which may also decrease the incidence of postherpetic neuralgia.


Figure 19.8 Varicella (Chickenpox)

Varicella, or chickenpox, presents with a low-grade fever and fatigue, followed by a scarlatina-form rash and subsequently clear teardrop vesicles on an erythematous base. The contents of the vesicles become cloudy over several days and then break open and form crusting. The lesions typically start on the trunk and spread to the face, and can involve the eyelids and conjunctiva, usually at the limbus. Varicella keratitis presents as superficial punctate keratopathy with possible dendrites, which is similar to herpes simplex virus type I. Other ocular manifestations of varicella include interstitial keratitis, neurotrophic corneal ulcers, external ophthalmoplegia, cataract chorioretinitis, and optic neuritis. Intrauterine varicella infection can lead to retinochoroidal lesions (right image), cutaneous scars, and other malformations.


Figure 19.9 Cytomegalovirus (CMV)—Congenital Maculitis

CMV retinitis will occur in a small percentage of patients with congenital CMV. The necrotic retinitis has a predilection for the macula. Patients may develop low-grade fever, headache, myalgia, and sore throat. In rare circumstances, especially in immunocompromised children, acquired CMV can cause meningitis and encephalitis, esophagitis, myocarditis, or interstitial pneumonia; CMV retinitis and potential vision loss may also develop. Patients with CMV retinitis should be treated with intravitreal ganciclovir or foscarnet. Both agents have been demonstrated to decrease the progression and complications of CMV retinitis.




Figure 19.10 Congenital Cytomegalovirus (CMV)

Infants who are infected during gestation can have severe congenital abnormalities and possibly die. Patients who are immunocompromised, such as those with AIDS, can have significant retinitis. Congenital CMV is the most common intrauterine infection and affects approximately 1% of all newborns. Patients can present with mental retardation, seizures, hearing loss, and intracranial calcifications.


Figure 19.11 Acquired Cytomegalovirus (CMV) Retinitis

Retinal CMV infection is largely confined to children with AIDS and other forms of immunodeficiency with significantly depressed T-cell counts. The frequency of CMV in pediatric AIDS is much lower than seen in adults. Routine serial screening is not required. Unlike congenital CMV (Fig. 19.10), this necrotic retinitis has a predilection for the periphery of the retina and progresses to involve the macula and optic nerve. The infection does respond well to systemic parenteral treatment, but maintenance is required to prevent recurrence unless immunocompetency is restored, for example, with bone marrow transplantation for severe combined immune deficiency syndrome.


Figure 19.12 Candida

Candida albicans is a dimorphic yeast that is commonly found in the environment. Candida is not considered to be normal skin flora. However, it can colonize in the gastrointestinal tract or vagina in situations of increased temperature and humidity. Candidal infections may also involve the nails (left image), bloodstream, and ocular structures. The most common digit to be involved is the thumb, especially in children who suck their thumb. Candida albicans may also form a plaque-like material on the tongue and gums (oral thrush; right image). Ocular infection is rare in immunocompetent children.




Figure 19.13 Candida Lens Abscess

A rare complication of Candida endophthalmitis is involvement of the lens or anterior chamber structures. This is most often seen in septic premature infants with a persistent tunica vasculosa lentis (Chapter 7: Lens, Fig. 7.2). Systemic treatment for Candida is the first line of treatment: Intravenous amphotericin B with or without flucytosine. Lens extraction can then be performed. In patients with large amounts of vitreous inflammation, a vitrectomy can be performed to confirm the diagnosis, followed by intravitreal amphotericin B.


Figure 19.14 Retinal Candida

Endogenous candidal endophthalmitis is almost always associated with disseminated candidiasis with extensive tissue invasion in other organs, particularly the heart and kidney. Immunocompromised patients and patients with a contaminated indwelling catheter or endotracheal tube have the greatest risk of developing endophthalmitis. In coherent individuals, the symptoms include floaters and loss of vision. Clinical examination shows multiple discrete white fundi with an overlying vitreous reaction. These lesions usually respond well to intravenous agents.


Figure 19.15 Tuberculosis

Tuberculosis is a disease caused by infection with Mycobacterium tuberculosis. Tuberculosis typically affects the lungs and is more common in immunocompromised patients. Clinical manifestations of tuberculosis primarily affect the respiratory system. Most patients with primary pulmonary tuberculosis are asymptomatic and are detected on tuberculin skin test or abnormal chest radiograph. Definitive diagnosis may require morning gastric lavage for acid fast stain and culture. Extrapulmonary tuberculosis can involve any organ system via hematogenous spread.


Figure 19.16 Tuberculosis Retinitis and Optic Nerve Infiltration

The ocular manifestations of tuberculosis include uveitis and retinitis. This patient has retinal lesions. Patients may also present with vision loss secondary to infiltration of the optic nerve and optic nerve inflammation as shown here. Typically there is a focal lesion that does not have an overlying vitreitis or associated uveitis. Ocular manifestations of tuberculosis respond well to systemic treatment.


Figure 19.17 Tuberculosis Phlyctenule

Worldwide, tuberculosis is the most common cause of phlyctenule. Usually presenting as a solitary white peripheral corneal lesion that may be raised and/or vascularized, (arrow) tuberculosis phlyctenule is an immunologic response to Mycobacterium. Histologically, the lesion is a collection of white blood cells. Treatment requires systemic antituberculosis therapy with topical measures for comfort and reduction of the often-present uveitis. This patient has a stromal scar at the site of her phlyctenule.


Figure 19.18 Pertussis

Pertussis, or whooping cough, is caused by a Gram-negative coccobacillus Bordetella pertussis. Clinical manifestations include repetitive forceful coughing with a subsequent large inspiratory effort, which creates the whooping sound as the inhaled air travels through the narrowed pharynx. This photograph shows a patient with subconjunctival hemorrhage secondary to Valsalva. Increased venous pressure during the coughing episodes can cause rupture of subconjunctival capillaries and result in significant subconjunctival hemorrhage. Treatment is not indicated unless there is significant conjunctival exposure and dryness and would include artificial tears and lubrication.


Figure 19.19 Leprosy

Leprosy is caused by infection with Mycobacterium leprae. The most commonly involved areas include the peripheral nervous system and skin. Ocular involvement is uncommon. This photograph shows a lesion of the right brow. This represents erythema nodosum leprosum, and consists of a tender nodule. This lesion will typically grow if not treated with appropriate systemic therapy. Treatment options include dapsone, rifampin, and clofazimine. Other ocular manifestations of leprosy include prominent corneal nerves, superficial punctate keratopathy, conjunctivitis, and uveitis.