Fig. 12.1
Purulent conjunctivitis due to gonorrhea infection
Diagnosis
For ocular disease, culture from conjunctival exudates is the gold standard for diagnosis of gonoccal infections. Colonies grow within 24–48 h of inoculation but generally gonorrhea tends to be difficult to culture. It is important to plate the secretions immediately onto chocolate agar for best results [5]. Gram stain as has good sensitivity for gonococcal infection, but does not confirm diagnosis . Nucleic acid amplification tests (NAATs) are useful for urogenital infection [5].
Management
A single IM dose of ceftriaxone is the treatment of choice for gonococcal ophthalmia neonatorum, along with eye irrigation with saline solution at frequent intervals until the discharge has resolved. Topical antibiotic treatment is unnecessary when systemic treatment is given [25].
In the United States, prophylaxis for gonococcal ophthalmia neonatorum is recommend in all infants and required by law in many states. Medication is applied topically within 1 h after birth. Prophylactic medications include 1 % silver nitrate solution, 1 % tetracycline ointment, or 0.5 % erythromycin ointment, however topical silver nitrate and tetracycline are no longer manufactured in the U.S. [25, 26]. Infants born to mothers with known gonococcal infection should be treated with a single parenteral dose of a 3rd generation cephalosporin due to the potential for failure of prophylaxis [25].
Leprosy
Definition
Leprosy, also known as Hansen’s disease , is a chronic, granulomatous infectious disease caused by the acid-fast bacillus Mycobacterium leprae . The bacterium is transmitted from person-to-person through droplet exposure. It is a slowly replicating bacterium, with an incubation period of about 5 years. It can take up to 20 years for symptoms of the disease to actually appear. Leprosy is disease of the skin , peripheral nerves, and mucus membranes caused by infiltration of the bacterium in these locations [27].
Epidemiology
Worldwide, 200,000–300,000 patients are blind from leprosy [28]. At the end of 2012, official figures from 115 countries reported a registered global prevalence of leprosy at 189,018 with 232,857 new cases reported during the same year. Leprosy is exceedingly rare in the United States, but is highly endemic in the following countries: Angola, Bangladesh, Brazil, China, Democratic Republic of Congo, Ethiopia, India, Indonesia, Madagascar, Mozambique, Myanmar, Nepal, Nigeria, Philippines, South Sudan, Sri Lanka, Sudan and the United Republic of Tanzania [27]. Even in highly endemic areas, the bacterium has low pathogenicity. Only 5 % of people exposed to the bacterium eventually develop disease. The remaining 95 % show resistance to the disease [29].
Systemic Manifestations
Clinical manifestations of leprosy depend on the patient’s immune response. There are two clinical forms of leprosy, lepromatous and tuberculoid, however patients can also have overlap between these two types. In tuberculoid leprosy, patients have a vigorous cellular immune response that limits the disease to a few, defined skin patches or nerve trunks. In lepromatous disease there is an absence of a specific cellular immune response to the bacterium, thus allowing for uncontrolled proliferation of the bacterium resulting in many lesions and extensive infiltration of the skin and nerves [30].
Skin lesions most commonly manifest as hypopigmented, and sometimes erythematous, macules or plaques with a raised edge, often with reduced sensation. Nerve infiltration and damage occurs in the peripheral nerve trunks and the small dermal nerves. Involvement of nerves causes nerve enlargement, with or without tenderness, and regional patterns of sensory or motor loss. Small dermal and autonomic nerve involvement causes hypoaestheisa, anhidrosis, and can cause a stocking-glove sensory loss [30].
Ophthalmic Manifestations
Along with systemic findings, patients with leprosy involving the eye will present with reduced visual acuity or even blindness [27].
Leprosy affects the eye through direct infection of the bacterium in the skin of the eyelids, tear ducts, and lacrimal glands, facial nerve, ophthalmic division of the trigeminal nerve, or direct invasion of the anterior segment [28].
Adnexal manifestation includes madarosis of the eyelashes and eyebrows, lagophthalmos (due to facial nerve infiltration), entropion, ectropion, trichiasis, and low lacrimal secretion. Anterior segment findings include conjunctivitis, decreased corneal sensation (due to trigeminal nerve involvement), exposure keratitis , corneal opacities, iris nodules, iris atrophy, anterior uveitis, episcleritis, and scleritis [28, 29]. Thickening and beading of corneal nerves is detected on slit lamp exam and is a common and characteristic finding in early leprosy [31]. The posterior segment involvement , very rare in leprosy, manifests as minute, white, “pearl-like” choroidal nodules, similar to those seen in the iris [29, 31].
Diagnosis
Diagnosis of leprosy is principally based on clinical signs and symptoms. Smears of affected skin can be performed to detect the presence of acid-fast bacilli. In endemic regions, a patient is regarded as having leprosy if he or she has the following:
- 1.
Hypopigmented or reddish skin lesions with loss of sensation
- 2.
Involvement of the peripheral nerves, indicated by loss of sensation and weakness in the muscles of the hands, feet, or face
- 3.
Skin smear positive for acid-fast bacilli [27]
Management
For treatment purposes, leprosy is classified as multibacillary (more than 5 lesions), puacibacillary (2–5 lesions), or a single-lesion disease [30].
The World Health Organization recommends a multidrug antibiotic regimen for the treatment of leprosy, which includes a combination of rifampin, clofazamin, and dapsone for 12 months in patients with multibacillary leprosy or a combination of rifampin and dapsone for 6 months in patients with paucibacillary leprosy. Patients with single lesion leprosy can be treated with a one-time dose of rifampin, ofloxacin, and minocycline taken together [27].
Facial nerve paralysis causing lagophthalmos with onset within 6 months can be treated with oral corticosteroids. The patient should be instructed to tape the eyelids closed, lubricate corneal and consider an eye patch/shield to protect the eye for exposure. Uveitis should be treated with topical corticosteroids and mydriatics. Corneal abrasions, keratitis, or ulcers caused by exposure should be treated as usual with lubrication and topical antibiotics [27].
Tuberculosis
Definition
Epidemiology
The World Health Organization estimates approximately one-third of the world population is latently infected with Tb, with >9 million cases of active tuberculosis yearly [33]. China, India, and the African continent account for the largest number of new and recurrent cases. The incidence of tuberculosis in the United States in 2011 was 3.4 cases per 100,000 people, with immigrants and ethnic minorities being disproportionately affected. The highest incidence in the U.S. is among Asians. Approximately 79 % of foreign-born people with Tb were diagnosed after being in the U.S. more than 2 years, consistent with reactivation of latent disease. In the U.S., tuberculosis has reemerged as a public health problem due to the AIDS epidemic [32]. Eighty-one percent of those diagnosed in 2011 were HIV-positive [34].
Uveitis due to systemic Tb infection varies around the world. Eye involvement in patients with systemic Tb ranges from 0.14 to 10 % of patients with Tb in India, 1 % in the United States, 4 % in China, 6 % in Italy, 7 % in Japan, and 16 % of patients in Saudi Arabia [33].
Systemic Manifestations
Systemic disease can occur after primary exposure, but in 90 % of cases it occurs secondarily after reactivation of the disease. The great majority of patients mount an immune response upon initial infection leading to the formation of pulmonary caseous granulomas that contain, but do not eliminate, the infection. A small proportion of the bacteria live in a dormant state within these granulomas and can be reactivated later in life. In an immunocompetent individual, the risk of reactivation is 10 % over the course of a lifetime. The risk of reactivation is even higher, 10 % yearly, in a patient with HIV [33].
The most common manifestation of reactivated tuberculosis infection is granulomatous lung disease, seen in 80 % of patients with reactivation. Extra-pulmonary tuberculosis can manifest in the gastrointestinal tract, cardiovascular system, musculoskeletal system, genitourinary system, central nervous system, as well as the eyes [32]. Miliary Tb most commonly occurs in immunocompromised patients, and represents unchecked hematogenous dissemination of the infection in primary or secondary disease.
Ophthalmic Manifestations
Ocular manifestations of Tb can result from active infection or from an immunologic reaction to the organism [32]. Tuberculosis can affect the anterior and posterior segment of the eye, as well as the orbit. Presentation of Tb is extremely varied and it can present as an acute anterior uveitis, chronic granulomatous anterior uveitis with mutton fat keratic precipitates, an intermediate uveitis, vitritis, macular edema, retinal vasculitis, neuroretinitis, multifocal choroiditis, subretinal abscess, endophthalmitis, and panophthalmitis [32]. Tb has also been associated with necrotizing and non-necrotizing diffuse or nodular scleritis, epscleritis, and peripheral ulcerative keratitis. Rarely, Tb associated inflammation presents as an interstitial keratitis , phylyctenulosis, iris or ciliary body granulomas, and dacroadenitis [34]. Among these manifestations, the most common clinical finding is posterior uveitis [32, 34]. Eales disease , classically thought to be an idiopathic retinal vasculitis, is now considered to represent a hypersensitivity reaction to tuberculous antigens. It is characterized by a peripheral ischemic vasculitis with neovascularization and recurrent vitreous hemorrhage without other signs of inflammation, and is typically seen in young men where tuberculosis is endemic [33].
Tuberculous choroidal granulomas (tuberculomas) occur in association with pulmonary and non-pulmonary systemic disease. They are usually white, cream, or yellow in appearance and can be unifocal or multifocal. Visual symptoms depend on location and extent of the tuberculomas. Systemic symptoms such as fever, malaise, cough, hemoptysis, and weight loss are helpful in alerting the clinician toward TB as the cause [34].
Diagnosis
A tuberculin skin test (TST) or serum quantiFERON-TB Gold testing can help aid in the diagnosis of ocular tuberculosis. However, neither of these tests is diagnostic for tuberculosis eye disease and the clinician must rule out other potential infectious or inflammatory causes of uveitis (such as sarcoidosis) on the differential before designating a diagnosis of ocular Tb. The gold standard for diagnosis of ocular Tb is a positive culture from ocular tissue or fluid, although this may be difficult to obtain in many cases. PCR testing on ocular tissue or fluid for Tb has low sensitivity, possibly due to a low bacterial load in ocular fluids and a thick cell wall of M. tuberculosis [34]. Chest X-ray or chest computed tomography can help in the cases of suspected ocular TB as it can reveal pulmonary lesions and lymphadenopathy [32].
Fluorescein angiography has an important role in the evaluation of a patient with suspected ocular tuberculosis. It is very sensitive in picking up evidence of retinal vasculitis, and often shows that vasculitis is more extensive than indicated by clinical examination. Macular edema, optic disc edema, and choroiditis are other potential angiographic findings [32].
Management
Treatment for ocular Tb is directed at both the inflammatory and infectious components of the disease. Multi-drug therapy with isoniazide, rifampin, ethambutol, and pyrazinamide initially for 2 months, followed by rifampin isoniazide for an additional 4–7 months is recommended. Systemic corticosteroid therapy (oral prednisone at 1 mg/kg/day) and topical steroids and cycloplegics are used in conjunction with antimicrobial therapy to treat the inflammatory response [32].
Group B Streptococcal Infections
Definition
Group B streptococcus, also known as Streptococcus agalactiae , is a gram positive cocci that is a major infectious cause of neonatal obidity and mortality. In the U.S., universal screening guidelines have been in place by the CDC since 2002 to identify mothers to receive intrapartum antibiotics in order to reduce the transmission of the bacteria to neonates and reduce the neonatal infection [35]. Pregnant women are routinely screened for GBS colonization between 35 and 37 weeks of gestation. If testing is positive, they are treated with intravenous antibiotics during delivery [36].
History Related to Eye Findings
Ocular infection with GBS is extremely rare in neonates. Neonates with ocular involvement of GBS will have mothers who tested positive on screening prenatally. Most cases present with coincident sepsis or meningitis. Patients may present with conjunctival injection, periorbital edema/erythema, corneal edema or opacity, elevated intraocular pressure, iris neovascularization, or leukocoria mimicking retino-blastoma [36].
Epidemiology
Prior to perinatal preventative strategies, the incidence of early-onset neonatal infection with group B strep was 0.47/1000 live births (between 1991 and 2001). It has since declined to about 0.3/1000 live births in the following years. Despite this reduction, neonatal GBS is still the leading cause of serious neonatal infection resulting in significant morbidity and mortality [35].
The GBS colonization rate in pregnant women varies from 15 to 35 %. Risk factors for neonatal infection include positive vaginal cultures in the mother, bacteriuria during pregnancy, low-birth weight, preterm gestation, rupture of membranes >18 h, intrapartum fever, chorioamnionitis, previous infant with GBS disease, intrauterine fetal monitoring, and low levels of maternal anticapsular antibody [35].
Systemic Manifestations
Group B strep is a major cause of neonatal infection. It can present as an early-onset sepsis in the first days of life as well as a late-onset sepsis, which is into the first month or two of life. Presenting features of infants with GBS sepsis include respiratory distress or apnea, lethargy, refusal to feed, temperature instability, poor perfusion, hyperbilirubinemia, skin rash, pneumonia, or meningitis [35].
Ophthalmic Manifestations
Most patients with ocular tuberculosis have no manifestation of systemic or pulmonary disease [32]. Ocular symptoms are varied and depend on the part of the eye that is involved. Patients can present with visual changes, pain, photophobia, and tearing [33].
GBS ocular infection presents as endogenous endophthalmitis. As of 2010, there were only 6 reported cases of GBS endogenous endophthalmitis in neonates reported in the literature. In 4 of these reported cases, the infant was also diagnosed with GBS meningitis [36].
Diagnosis
Diagnosis of GBS endophthalmitis can be confirmed through vitreal culture. It most reported cases, it was presumed as these patients either had confirmed GBS sepsis or meningitis through blood and CSF cultures, respectively [36].
Management
As GBS endophthalmatis in neonates is very rare, there is no defined protocol for treatment. The few reported cases infants have been treated in varying ways. Nearly all infants were treated with systemic, intravenous antibiotics, which included a broad-spectrum penicillin and an aminoglycoside. Many also received intravitreal injection with vancomycin and ceftazidime. In cases where retinoblastoma could not be ruled out or the patient had a blind, painful eye, the eye was enucleated [36].
Parasites
Baylisascaris Infections
Definition
Baylisascariasis is caused by infection by the nematode parasite Baylisascaris procyonis . The definite host for this parasite is the American raccoon. Infection occurs in humans after consumption of the parasite egg, which hatches in the intestine. Hatched larvae penetrate the gut wall and migrate to other organs after entering the blood stream through the portal system [37].
Epidemiology
Baylisascaris is indigenous in North American raccoons, but occurs in raccoons all across the world. In North America, the prevalence of Baylisascaris in raccoons is highest in the Midwest, northeast, and West Coast raccoon populations [37].
The most important risk factors for infection include pica or geophagia, and exposure to raccoons or environments contaminated with raccoon feces, which contain the parasite eggs [37].
Systemic Manifestations
Infection of organs other than the eye and heart is known as visceral larva migrans (VLM) , and is caused by migration of hatched larva to various organs of the human body. Infection causes granuloma formation, which have histologically been found in the heart, mediastinal soft tissues, pleura and lungs, small and large bowel walls, and mesentery and mesenteric lymph nodes. Presentation includes nonspecific clinical findings such as a macular rash most commonly on the face and trunk, hepatomegaly, and pneumonitis with dyspnea and tachypnea [37].
In its most severe form, B. procyonis is a rare cause of fatal or neurologically devastating neural larva migrans (NLM) in infants and young children, characteristically presenting as an acute, fulminant eosinophilic meningoencephalitis [37].
Ophthalmic Manifestations
Patients infected with Baylisacaris will present with diffuse unilateral subacute neuroretinitis (DUSN) and complain of progressive visual impairment, often unilateral. In those with isolated ocular disease, there is commonly no known exposure to raccoons or raccoon feces, indicating that disease occurs after ingestion of a small number of eggs followed by chance migration of a single larva to the eye [37].
DUSN can have an insidious onset. Early symptoms may include a unilateral paracentral or central scotoma, pain, discomfort, or transient visual obscurations. Patients usually have good general health [38].
Ocular disease (Ocular larva migrans, OLM ) occurs in both adults and children. It can be an isolated finding or associated with NLM and VLM [37].
Most infants and children with NLM or VLM can develop visual impairment or blindness from invasion of larva into the visual cortex or into the eye itself [37].
Patients with DUSN have a variety of findings that can cause visual loss including vitritis, choroidioretinitis, optic neuritis or atrophy, papillitis, and crops of multiple evanescent, gray‐white outer retinal lesions. In the late stages, optic atrophy, retinal artery narrowing, diffuse pigment epithelial degeneration, and an abnormal electroretinogram can be seen [40]. Late features of DUSN can include retinal narrowing, optic nerve atrophy, and focal or diffuse retinal pigment epithelium atrophy [38]. Ophthalmic exam can sometimes reveal a migrating larvae within the retina (Fig. 12.2). Visible Baylisascaris in the retina is larger in size than Toxocara, another common cause of OLM (1000–2000 × 60–70 μm vs. 350–445 × 20 μm, respectively).
Fig. 12.2
Subretinal larvae seen in DUSN (photo courtesy of Scott Oliver, MD)
Eighty percent of patients with late stage DUSN have profoundly decreased vision at 20/200 or worse [40].
Diagnosis
Diagnosis is mainly clinical, based on signs/symptoms, along with evidence of eosinophilia. Serologic testing showing the presence of anti-Baylisascaris antibodies in the CSF or serum is supportive of the diagnosis [37].
Management
OLM and DUSN have both been successfully treated with laser photocoagulation of the intraretinal larvae, however the worm is only visualized in 25–40 % of cases [41]. Systemic steroids are used to reduce any sequential intraocular inflammation. There is no one drug proven to be effective in treating Baylisascariasis [5]. The role of anti-helminthics in ocular disease has not been established [37].
Toxocariasis
Definition
Toxocariasis is a parasitic infection caused by the roundworm species Toxocara. The definitive host of this species is the common house cat (Toxocara cati) and dogs (Toxocara cani). Infection in humans occurs after ingestion of material contaminated with parasite eggs. The eggs hatch in the intestines then migrate to tissues throughout the body [42].
Epidemiology
Ocular Toxocara primarily affects children, with geophagia and dog-ownership being significant risk factors. Most children present in late childhood or in adolescence [42].
Systemic Manifestations
As with Baylisascaris infection, systemic infection with Toxocara is also termed visceral larva migrans (VLM) . Systemic disease is characterized by fever, malaise, hepatomegaly, rash, and leukocytosis [42].
Ophthalmic Manifestations
Patients usually present with monocular visual loss. Visual acuity can be severe, as low as 20/200 or less in many cases. Toxocariasis is an important diagnosis to consider in patients who present with leukocoria and can have presentation similar to retinoblastoma. The most common clinical findings include diminished vision, leukocoria, vitritis, ocular injection, and strabismus [42].
Toxocara is another parasitic infection that causes ocular larva migrans (OLM ), which occurs when the parasite infiltrates the eye and causes and inflammatory reaction. It occurs unilaterally in 90 % of cases.
Clinical presentation can be classified into four forms: a posterior pole granuloma, peripheral granuloma, nematode endophthalmitis, or an atypical presentation. The posterior pole granuloma is the most common form of presentation (Fig. 12.3), and is characterized by a focal, whitish subretinal or intraretinal inflammatory mass in the posterior pole, with or without signs of acute inflammation. Peripheral granulomas appear as focal, white, elevated nodules in the periphery, which may have surrounding inflammatory membranes or pigmentary changes.
Fig. 12.3
White, posterior pole granuloma in patient with toxocariasis (photo courtesy of Scott Oliver, MD)
Toxocara endophthalmitis is a panuveitis and involves a prolonged course of inflammation caused by the intraocular nematode. It manifests as a red, painful eye with diffuse inflammation, and retinal exam may reveal a granuloma and tractional inflammatory membranes.
Atypical presentations include papillitis, optic nerve head edema, motile subretinal larvae, diffuse chorioretinitis, conjunctivitis, keratitis , iridocyclitis, focal iris nodules, and cataract [43].
Diagnosis
Serologic testing with ELISA for the Toxocara excretory secretory IgG has a reported 90 % sensitivity and specificity for systemic infection. ELISA studies can be performed on aqueous or vitreous samples as well. However, ocular toxocariasis is primarily a clinical diagnosis, and only histopathologic evaluation of an enucleated eye will reveal larvae [42].
Management
Ocular inflammation is routinely managed with topical, periocular, or systemic corticosteroids. Cycloplegics may be used if anterior segment inflammation is present. The need for systemic antihelmenthics is unclear. However, the use of antihelminthic drugs, such as albendazole, in combination with corticosteroids has shown favorable outcomes in some studies [43]. Vitreoretinal surgery is indicated in patients with retinal detachments caused by tractional membranes [42].
Toxoplasmosis
Definition
Toxoplasmosis is infection caused by the protozoan Toxoplasma gondii . Felines are the primary host of T. gondii. The organism is transmitted to humans orally after handling or eating raw meat that harbors tissue cysts or by drinking water or contaminated food with parasite oocysts. Congenital infection occurs through vertical transmission from an acutely infected mother transplacentally to the fetus. The risk of congenital toxoplasmosis is highest in the third trimester, whereas clinical manifestations are more severe if acquired during the first trimester [44].
Epidemiology
In 2004, it was estimated that that up to one-third of the world’s population was infected with Toxoplasma gondii ; however, there is significant geographic variation in seroprevalance. Prevelance of T. gondii IgG positivity among U.S. born subjects between 1999 and 2004 was estimated to be about 9 %. Multiple studies performed in various countries have identified toxoplasmosis as the most common cause of posterior uveitis [44].
The incidence of congenital toxoplasmosis varies geographically. In the U.S., it is estimated to occur in 1 in 10,000 live births, with the incidence ocular disease being reported to be as high as 75–94 % of these cases. Ocular disease is the most common manifestation of congenital toxoplasmosis [44].
Systemic Manifestations
Immunocompetent people who acquire toxoplasmosis usually do not have any other systemic findings other than asymptomatic cervical lymphadenopathy. Roughly 10 % of otherwise healthy people who are infected with toxoplasmosis will report non-specific symptoms such as myalgias, fevers, and fatigue. Infection in immunocompromised individuals most commonly presents as a fatal encephalitis, but may also manifest as a pneumonitis or septic shock [45].
Congenital toxoplasmosis can cause spontaneous abortion, or the child may be born with hydrocephalus, microcephaly, intracranial calcifications, epilepsy, psychomotor retardation, and leukopenia [45] (Fig. 12.4).
Fig. 12.4
Macular scarring seen in congenital toxoplasmosis (photo courtesy of Scott Oliver, MD)
Ophthalmic Manifestations
The most common clinical presentation of toxoplasmosis is eye involvement, presenting as a retinochoroiditis [44]. The classic finding ocular finding is a fluffy, white area of retinochoroiditis or necrotizing retinitis adjacent to a chorioretinal scar (Fig. 12.5). Patients will typically also have a vitritis, causing a “headlight in the fog” appearance. Atypical presentations can manifest as retinal vasculitis, granulomatous or nongranulomatous anterior uveitis, or papillitis [45]. Ocular disease may be asymptomatic in young children. Verbal children may note decreased vision or eye pain, while parents may notice leukocoria or strabismus [45].
Fig. 12.5
Classic white area of retinitis adjacent to chorioretinal scar in reactivated toxoplasmosis (photo courtesy of Scott Oliver, MD)
Diagnosis
In the majority of cases, the diagnosis of ocular toxoplasmosis is made by observation of the classic clinical findings described above. PCR or antibody testing can be performed on ocular fluid in atypical or unclear cases. Serologic testing for T. gondii antibodies has little role in the diagnosis of ocular toxoplasmosis due to high rate of seropositivity in the general population [45].
Management
With or without treatment, the active retinochoroiditis caused by toxoplasmosis resolves within 1–2 months in immunocompetent individuals. There is currently no drug available that is known to completely cure infection in humans. Thus, the goal of antimicrobial therapy is to limit parasite replication in active retinochoroiditis. Most ophthalmologists will treat patients with reduced vision, a lesion located within the arcades or near the optic disc, or those with significant vitreous haze. Infection in immunocompromised patients and atypical presentations also warrant treatment. The classic treatment includes pyrimethamine orally, sulfadiazine, and systemic corticosteroid. Folinic acid should be used to avoid toxicity related to pyrimethamine. An alternative treatment option is trimethoprim-sulfamethoxazole and systemic corticosteroid. Corticosteroids should be omitted in immunocompromised patients, and these patients should remain on prophylactic therapy (often with trimethoprim-sulfamethoxazole) while in an immunocompromised state [45].
Cysticercosis
Definition
Cysticercosis is a parasitic infection caused by the pork tapeworm, Taenia solium . The parasite exists as a cyst in pig, the intermediate host, and as worm in humans, the definitive host. Humans become infected after eating raw pork or consuming water or food contaminated with fecal matter [46]. Ingested eggs hatch in the intestines, migrate across the intestinal wall into the blood stream or lymphatic system. The parasite travels throughout the body, infecting the central nervous system, eyes, and/or muscles and cysts within these tissues [47].
Epidemiology
Systemic Manifestations
There are two clinical forms of cysticercosis. In focal cysticercosis, the parasite invades the muscles or perimuscular tissue only. The other form is systemic or central nervous system disease [47].
Cysts within the brain and spinal cord cause the most severe form of the disease, called neurocysticercosis . This may be asymptomatic, or cause seizures, headaches, confusion, difficulty with balance, cerebral edema, hydrocephalus, stroke, or death. Cysts in the muscles are usually asymptomatic , but can cause tender lumps under the skin [47].
Ophthalmic Manifestations
Intraocular cysticercosis is a manifestation of systemic disease, while orbital/adnexal cysticercosis is a manifestation of focal disease. T. solium reaches the eye via the posterior ciliary vessels and nerves [47].
Patients with intraocular disease may present with loss of visual acuity, scotoma, or eye pain. Many will also have coincident central nervous system disease. In orbital or adnexal disease, symptoms depend on the size and location of the cyst [46].
The most common form seen in children is orbital/adnexal cysticercosis. The most common site of cyst formation include the extraocular muscles, subconjunctival space, eyelid, optic nerve, retro-orbital space, and lacrimal gland [47] (Fig. 12.6).
Fig. 12.6
Left: Fundus photo demonstrating subretinal cyst from cystercercosis with white scolex centrally. Right: axial FLAIR MRI sequence demonstrating multiple cystic lesions in the brain due to neurocystercercosis
Intraocular cysticercosis is characterized by cysts floating in the anterior chamber or vitreous, or posteriorly lodged in the subretinal space. Visual loss occurs if there is macular involvement. Death of the encysted parasites incites a severe inflammatory response and scarring, leading to scarring and possible visual loss [47]. Often, fundus examination is difficult due to the presence of significant vitritis and vitreous opacities. B-scan is routinely warranted and allows visualization of the cyst wall and the parasite within the cyst. Stimulation of parasite with light can elicit movement [46].
Diagnosis
Diagnosis is made by direct visualization of the cyst on tissue biopsy or inside the eye, or with cyst movement on B-scan. It can also be confirmed by serum antibodies or by parasite detection in the stool, either by direct visualization or by antigen testing [47].
Stool is not a sensitive way to diagnose cysticsercosis, so a negative result will not rule out cysticercosis infection of the eye.
Management
For orbital or adnexal disease, surgical removal of the cyst is the treatment of choice for accessible lesions. Lesions that cannot be surgically removed are treated systemically with Praziquantel (50 mg/kg/day) along with corticosteroids to reduce inflammation [47].
Antihelminthic therapy is not recommended for patients with intraocular disease, as it can precipitate severe inflammation, causing inflammatory phthisis or severe visual loss. The treatment of choice is surgical removal of the encysted parasite [47].
If patients present with intraocular and systemic disease, which is often the case, the surgical removal of the parasite should be performed before systemic treatment. Thus a thorough eye exam is recommended prior to the initiation of antihelminthic treatment in patients with neuro-cysticercosis.
Onchocerciasis (River Blindness, Filariasis)
Definition
Onchocerciasis, also known as river blindness and Robles disease, is caused by the nematode Onchocerca volvulus . The parasite is transmitted to humans by the bite of Simulium exiguum, also known as the black fly. Adult female worms are transmitted from the bite into the subcutaneous tissue, where the worm lays eggs. The eggs hatch into microfilaria [46].
Epidemiology
The World Health Organization estimates that onchocerciasis is the second leading cause of infectious blindness worldwide, with 17 million people infected, 270,000 of whom are blind and 500,000 of whom are visually impaired. 123 million people are at risk for becoming infected with the parasite [46, 49]. The disease is most prevalent in Africa, where 99 % of cases are seen and people in 28 countries are affected [50]. It is also found in Yemen and Central and South America [46].
Systemic Manifestations
Other than ocular involvement, onchocerciasis primarily affects the skin. Skin manifestations include acute and chronic papular dermatitis, scratch marks, lichenification, and pigmentary changes known as “leopard skin” [48].
Ophthalmic Manifestations
Individuals with ocular involvement will invariably have dermatologic involvement [48]. Ocular symptoms include visual impairment, including visual field loss and blindness, eye pain, irritation, and itching skin lesions [48, 49].
When deposited near the eye, the parasite migrates through the skin or bulbar conjunctiva into the cornea, anterior chamber, and iris. They enter the posterior chamber via the ciliary vessels and nerves. Dead or degenerating worms incite a severe inflammatory reaction leading to scarring and local inflammation, which can cause significant visual morbidity [46].
Ocular disease is classified into two types: savannah and rainforest. Blindness is more common in the savannah type, and is mainly caused by a punctate or sclerosing keratitis, snowflake corneal opacities, and iridocyclitis with a characteristic pear-shaped iris deformity (torpid iritis). In rainforest onchocerciasis, blindness is less common and is caused by posterior segment involvement, including peripheral chorioretinal lesions, vascular sheathing, and optic neuritis leading to optic atrophy. In addition to these ocular findings, microfilaria may be visualized in the cornea or anterior chamber on examination [46, 48].
Diagnosis
The diagnosis of onchocerciasis is confirmed by observation of live microfilaria in biopsy specimens of symptomatic skin nodules [46].
Management
Ivermectin, 150 mg/kg annually is the treatment of choice. Suramin may be used in cases that are resistant to ivermectin [46].
Phthiriasis Palpebrarum
Definition
Phithriasis palpebrarum is a rare parasitic infection of the eyelashes and eyelids caused by the pubic louse, Phthiriasis pubis, and its ova. Humans are the only host, and transmission is by direct human-to-human contact, although fomites, such as bedding and clothing may also play a role [51]. Because of its mode of transmission, a diagnosis of phithriasis palpebrarum in children should always raise concern for child abuse and involvement of child protective services may be warranted [52].
Epidemiology
Phithiriasis pubis infestation is found worldwide and occurs in all races and ethnic groups and all levels of society. Infestation of eyelashes or eyelids, however, is very rare. As noted above, when seen in children, it raises concern for sexual exposure or abuse [53].
Systemic Manifestations
Ophthalmic disease may be isolated, but individuals can also present with signs and symptoms of pubic involvement. The most common symptom is pruritis of the pubic and groin area [53].
Ophthalmic Manifestations
Presentation of ocular disease includes pruritus and irritation of the skin around the eye, including the lid margins and conjunctiva [52].
Ocular findings can include secondary blepharitis, follicular conjunctivitis, periauricular lymphadenopathy, and marginal keratitis . Examination may reveal conjunctival injection, eyelid erythema and swelling. Adult lice, nits (ova), and their excretions can be visualized at the base of the eyelashes [52].
Diagnosis
Diagnosis is based on clinical examination through observation of adult lice and nits on the eyelashes under magnification [52].
Management
There is no single treatment plan that has been determined to be optimal for the treatment of Phithriasis palpebrarum . Treatment should include mechanical removal of the lice and nits with jewelers forceps or plucking/trimming of the eyelashes. Additional treatment should include a topical pediculocidal agent, such as fluorescein 20 %, physostigmine, 0.25 %, mercuric oxide 1 % ophthalmic ointment and ammoniated mercury 3 % ophthalmic ointment, 1 % malathion drops or shampoo, and pilocarpine gel 4 %. Any ointment, including petroleum jelly or water-based gels, can be used to smother the lice. Treatment is recommended for 2 weeks, which corresponds to the life cycle of the louse [52]. Any items of close contact including bed sheets and clothing should be washed and dried at 50 °C or higher [52].
Viruses
Herpes Simplex Virus
Definition
Herpes simplex virus (HSV) is a double-stranded DNA virus. There are two types, HSV-1 and HSV-2. In general, infections with HSV-1 are above the waist and HSV-2 occur below the waist in sexually active individuals, however that is not an absolute and either virus can present in any location. All human herpes viruses establish latency and can reactivate. Reactivitation of HSV-1 and HSV-2 manifests as disease, typically vesicles in the oral or genital areas, or can be asymptomatic, typically shedding in the same areas. Additionally, HSV-1 and 2 can cause disseminated disease [5].
Epidemiology
HSV infections are ubiquitous with seropositivity of HSV-1 estimated to be over 25 % by the age of 7 [5] and between 50 and 90 % by adulthood [54, 55]. HSV is transmitted by direct contact from virus shed by HSV lesions or oral or genital secretions that harbor the virus. Thus, sexual abuse should be suspected in cases of HSV-2 infection in pre pubertal children.
It is estimated that 0.15 % of the US population experiences recurrent ocular infection due to the HSV virus [54]. Children have a worse visual prognosis due to corneal HSV infections than their adult counterparts due to a higher rate of late or missed diagnosis (up to 30 %) leading to more corneal scarring and amblyopia [56]. Additionally, children are more likely to have HSV recurrence, bilateral disease, and are more likely to have stromal keratitis than adults [56].
Intrauterine infections are rare, but can cause significant risk to sight due bilateral congenital cataracts, keratitis, conjunctivitis, and chorioretinitis. Neonatal infections are generally due to transmission of HSV-2 during birth and about 15–20 % of infants who have a neonatal HSV infection have some eye involvement [54].
Systemic Manifestations
Primary HSV-1 infection in an immunocompentent host is generally asymptomatic, but can sometimes cause pharyngitis, submandibular lymphadenopathy, and the classic gingivostomatitis. There is an incubation period of 2–14 days and then vesicles and fever develop. Symptoms resolve over the next 2 weeks. Recurrent HSV-1 infection is generally more mild and begins with paresthesias in the affected areas followed by vesicles and pain. It takes 3–10 days for the vesicles to crust and completely heal.
Primary HSV-2 infections incubate for about a week and are often asymptomatic. Similar to HSV-1, symptoms of a HSV-2 infection can include fever, lymphadenopathy and vesicle formation. Generally vesicles are in the genital area. Recurrent HSV-2 infections are also milder than primary infection.
Patients with neonatal HSV infection will present with symptoms between birth and 6 weeks of age. Twenty-five percent of patients with a neonatal infection have disseminated disease that can include liver, lung and central nervous system involvement. Less than half of patients with disseminated disease have only skin, eye and or mouth disease (SEM disease) and about 30 % of cases have CNS only disease [5]. Many of these patients who have disseminated HSV disease will present without the skin vesicles , making the initial diagnosis more difficult.
HSV encephalitis (HSE) can occur with primary or recurrent HSV-1 infection and can cause fever, altered mental status, and focual seizures. HSE tends to affect the temporal lobe and carries a very poor prognosis [5]. HSV can also cause meningitis or meningoencephalitis.
Ophthalmic Manifestations
Patients most commonly present with recurrent unilateral red eye associated with pain and photophobia. Patients can have a history of fever blisters/cold sores and many have a known diagnosis of HSV.
Primary eye infections usually present with a unilateral blepharoconjunctivitis with vesicles on the eyelid. Many children also have a follicular conjunctivitis. Epithelial keratitis presents in many patients with primary HSV-1 infection, often with a primary ocular infection. This is sometimes the typical dendrite, but can also be a superficial punctate keratitis, or geographic keratitis.
In recurrent ocular herpes, patient can have the epithelial keratitis as described above, but can also have a disciform keratitis, iridiocyclitis, increased IOP, or endotheliitis. Retinitis can also occur and cause acute retinal necrosis, but this is generally rare and generally present in the immunocompromised individual.
The edges of a herpetic corneal lesion tend to have heaped up edges with swollen epithelial cells that stain with Rose Bengal or Lissamine Green . Central ulcerated portion of the HSV lesion stains with fluorescein. It is important to check for decreased corneal sensation because this can predispose the patient to secondary bacterial infections and neurotrophic ulcers.
Interstitial keratitis is an uncommon complication and can occur in the presence of iritis or glaucoma. These patients have multiple or diffuse stromal infiltrates and may not have an overlying epithelial defect [57].
The uveitis associated with HSV infection typically is associated with an increased intraocular pressure, granulomatous keratic precipitates, and iris atrophy (Fig. 12.7).
Fig. 12.7
Left: external photo demonstrating synechiae and pigmented keratic precipitates in patient with HSV uveitis. Right shows transillumination defects in same patient
Diagnosis
Ocular HSV is usually diagnosed clinically, but cell culture, immunofluorescence, PCR, and the Tzanck smear can also be useful in the diagnosis. Serologic tests should be interpreted with caution as patients can be IgM positive with reactivitation disease and a high percentage of the population is positive serologically. Corneal or conjunctival scraping can be sent for viral culture [57].
Polymerase chain reaction (PCR) can detect HSV DNA in the CSF of neonates and older children with concerns for HSV meningoencephalitis. PCR of aqueous or vitreous fluid can be useful in certain cases.
Management
Congenital and neonatal herpes infections should be managed as an inpatient and treatment consists of intravenous acyclovir followed by long-term suppressive therapy. The duration of treatment depends on the type of infection (disseminated, skin-eye-mucous membrane, or CNS) and the long term suppressive therapy is typically a minimum of 6 months.
For eyelid and skin involvement, cool compresses as needed and topical antibiotic ointments to lesions can help with comfort. For any eyelid margin or conjunctival involvement, trifluridine or vidarabine ointment should be added.
HSV keratitis in a child can be treated with systemic acyclovir, topical trifluridine, or vidarabine ointment. Debridement of HSV epithelial lesions can promote healing, but may not be tolerated in the pediatric age group. In patients with stromal keratitis or uveitis, topical corticosteroids are indicated, but in patients with isolated epithelial disease, topical steroids are contraindicated.
Cycloplegics are indicated in patients with uveitis and can be helpful in patients with keratitis and photophobia [57].
The Herpetic Eye Disease Study Group was not designed to study the pediatric patient under 12 years old, but the results suggest that oral acyclovir helps prevent recurrent herpetic eye disease [58]. A period of acyclovir prophylaxis should be considered in children after serious disease and in recurrent disease, especially when it puts the child at risk for amblyopia or longer term vision problems .
Corneal scarring caused by herpes virus infection causes both deprivation and refractive amblyopia due to induced astigmatism, and the treatment of this amblyopia is important in restoring vision.
Varicella Zoster Virus
Definition
Varicella Zoster Virus (VZV) is also known as Human herpes virus type 3 . Primary infection with VZV causes varicella (also known as chicken pox). After primary infection or immunization, the virus remains dormant in the dorsal root ganglion. Reactivation infection is called shingles or zoster. When the reactivation infection occurs in the V1 distribution of the trigeminal nerve, it is called herpes zoster ophthalmicus (HZO) . This usually occurs along the frontal nerve when associated with HZO [5, 59].
Epidemiology
Humans are the only host of VZV. The typical incubation period before vesicles appears 0–14 days and the host is contagious for approximately 1–2 days before the vesicular rash begins. The virus is transmitted when virus particles are aerosolized from vesicles and also by respiratory secretions. The virus does not survive on fomites.
Prior to implementation of the VZV vaccine in the United States, varicella infection occurred mostly in children under the age of 10 and often in the late winter to early spring. The incidence of VZV was so high it was almost equal to the birth rate [59]. A single vaccination was recommended in 1995 and decreased the incidence of varicella in the United States decreased by 90 % between 1995 and 2005. The recommendation for a second dose of the vaccine in 2006 has further decreased the incidence of VZV in this country [5].
The incidence of Herpes Zoster is estimated to be about 1 million cases/year in the United States. Of those cases, about 10–20 % are cases of HZO [59]. The main risk factor for HZ is increased age. While immunosuppression is a risk factor, most (92 %) of patients who get HZ are immunocompetent [60]. Treatment of HZ can reduce HZO by 50 % [59]. It is still unclear how vaccination will affect the rates of HZ over a lifetime, and many other factors will also play into HZ incidence including increasing numbers of immunocompromised individuals, people living longer, and vaccines targeted at preventing herpes zoster.
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