reports of onchocerca chorioretinitis show pigmented cells in the retina, but without electron microscopy or immunohistochemistry, these cells have not be precisely identified [295, 299].

White intraretinal deposits are most numerous in patients who had extensive RPE and chorioretinal atrophy. These deposits were originally described in patients treated with diethylcarbamazine, but it is now believed that these changes can occur without treatment. The deposits tend to appear and disappear without sequelae within a period of 1 year [295]. Retinal pigment epithelial atrophy is not uncommon. It occurs either in a diffuse pattern characterized by areas of scattered loss of epithelium or in a geographic pattern where the areas of atrophy have well-defined borders.

Intraretinal microfilaria is commonly observed, and live microfilaria tends to move freely within the retina. Microfilaria is most easily observed when it is adjacent to retinal vessels or immediately under the internal limiting membrane [295]. Abnormalities such as epiretinal membrane, posterior vitreous detachment, and macular hole are seen frequently and appear to have higher frequency among patients with onchocercal chorioretinal disease [300, 301]. Cotton-wool spots have been rarely reported [295].

Bilateral optic atrophy associated with extensive RPE and chorioretinal atrophy have been reported. Sheathing of the retinal vessels at the disc can be seen in some patients [295].

16.4.2.2  Diagnosis and Treatment

Onchocerciasis can be diagnosed by the skin snip test. Skin snips are taken with a needle or a razor blade from skin nodules. Microfilaria can be identified and counted after examination of sectioned and stained ­tissue or a stained impression smear [302].

Ivermectin is the mainstay of treatment for onchocerciasis. It is effective in reducing the microfilarial load in the anterior chamber and in controlling anterior segment manifestations including keratitis and iritis, but it is not effective in the control of chorioretinitis [303– 305]. Hospital and community-based studies have shown this treatment to be associated with low morbidity, and the treatment rarely causes acute exacerbation of preexisting ocular lesions [306, 307], unlike with the previously available agents, suramin and diethylcarbamazine. Antimicroflorial agents are occasionally

associated with the Mazzoti reaction, a violent allergic reaction that, in severe cases, may lead to shock and coma. This reaction is usually accompanied with acute dermatitis, which may be limited to one or more extremities, headache, dizziness, and fever with general malaise. Corticosteroids and antihistamines are used to treat the reaction.

16.5  Bacterial Diseases

The last few decades have witnessed a change in the pattern of many infectious agents, including bacteria. Evolution of new infectious antibiotics, changes in host immune systems, and development of new modes of transmission may help to explain these changes. Out of the large number of bacteria that children and young adults are exposed to, few produce infectious disease. In this section, we discuss important bacterial infections that affect the eyes of children with emphasis on posterior segment manifestations.

16.5.1  Syphilis

Syphilis is a complex systemic infection, which is caused by treponema pallidum. Both congenital and acquired syphilis can produce ocular inflammatory manifestation.

T. Palladium is a small, slender, coiled bacterium. It is difficult to visualize by light microscopy and difficult to cultivate in vivo. The helical bacteria are 5–15 mm in length and are less than 0.18 mm in width. T. Pallidum does not grow in routine culture media but can remain mobile for several days in specific enriched culture media [308].

Syphilis is transmitted primarily by sexual intercourse but can occasionally be transmitted by contact with fresh blood or by accidental direct contact with infected mucocutaneous lesions. Following the widespread availability of antimicrobial drugs in the mid 1950s, there was marked decline in the number of cases of primary and secondary syphilis. Nevertheless, during the 1970s and 1980s, there was an increase in the number of reports of cases of congenital and acquired syphilis, perhaps related to increased incidence of transmission of syphilis through homosexual contact.

Heterosexual transmission, especially among medically underserved populations, is thought to have contributed to this rise as well [309]. Since 1985, there has been another large increase in the number of reported cases of syphilis among heterosexual men and women and of congenital syphilis [310].

16.5.1.1  Clinical Manifestations

Syphilis has been traditionally divided into three stages [311]. The primary stage is characterized by an ulcerative lesion (chancre), which appears approximately 3 weeks after exposure and heals spontaneously in immunocompetent patients within 3–6 weeks. The secondary stage appears approximately 6 weeks after the appearance of the chancre. Common signs of secondary syphilis include fever, malaise, and maculopapular skin rash. The secondary stage often subsides within weeks to months but can recur, typically within a year. Tertiary syphilis is characterized by gummatous lesions, which are necrotic lesions involving the skin, mucous membrane, bone, liver, and lung. Most late complications are the result of endarteritis obliterans involving the vasa vasorum of the aorta causing cardiovascular disease and of the central nervous system causing neurosyphilis.

The central nervous system can be involved in all stages of syphilis [312, 313]. Neurosyphilis can present in an active form with acute meningitis and cerebrovascular neurosyphilis or in a chronic form with generalized paralysis of insane or tabes dorsalis.

16.5.1.2  Congenital Syphilis

Congenital syphilis occurs to fetuses infected after 16 weeks of gestation. Before that time, transmission to the fetus can occur but does no harm to the developing child. The small size of the bacterium facilitates its passage through the placenta ,and almost all children born to mothers with primary syphilis acquired after the fourth month of pregnancy will develop congenital syphilis [314]. The risk of congenital syphilis is reduced for mothers having secondary syphilis and is further reduced for children born to mothers with latent syphilis. For unclear reasons, there has been increase in the number of reported cases of congenital syphilis

[315]. In order to gain control over this new epidemic, CDC recommended performing routine serological screening to pregnant women, particularly those at high risk and those living in areas with high incidence of syphilis [316, 317].

Congenital syphilis is associated with early manifestation occurring early in life or late manifestations occurring late in childhood. The late manifestations can occur due to ongoing inflammation or due to a hypersensitivity reaction. Traditionally, the distinction between early and late syphilis has been defined as 2 years of age [318]. With the recent epidemic of congenital syphilis and the high likelihood of ocular involvement, ophthalmologists are expected to play a large role in the diagnosis and management of the disease.

Early congenital syphilis presents mainly with a maculopapular rash and osteochondritis. Systemic involvement can cause an enlarged spleen or liver, producing jaundice, hematological abnormalities, generalized lymphadenopathy, and nephrosis.

Mucous patches may involve the conjunctiva or caruncle. Interstitial keratitis is a common occurrence. The triad of interstitial keratitis, deafness, and dental abnormalities are highly indicative of congenital syphilis. Limbal episcleritis and scleritis may occur in late congenital syphilis [319]. Congenital cataract may occur secondary to uveitis in early and late congenital syphilis, and ectopia lentis has been reported [320]. Acute iritis is a very common feature of early congenital syphilis, also occurring in late congenital syphilis. Secondary glaucoma may develop as a complication of uveitis.

Early and late congenital syphilis may present with periostitis causing orbital deformities, nasolacrimal duct stenosis, and dacryoadenitis. Cicatricial lids changes and other lid deformities may develop [321].

Posterior segment inflammation starts pathologically as multiple areas of inflammation of the choriocapillaris and typically does not result in recognizable disease. During the late stages of the disease, the lesions become clinically recognizable with the appearance of multiple scattered patches of choroidal ­atrophy, ultimately leading to the development of hypopigmented retinal scars. Attenuation of the blood vessels with clumping and localized proliferation of the retinal pigment epithelium causing a pseudoretinitis pigmentosa picture is seen. Alternation between the hypopigmented

and the hyperpigmented areas results in a pepper and salt fundus that mimics that of congenital rubella and can be diffuse or localized. Vascular sheathing or optic atrophy may be present, and vision loss can result from optics atrophy or epiretinal gliosis.

16.5.1.3  Acquired Syphilis

The ocular manifestations of acquired syphilis include a variety of anterior segment abnormalities, including gumma of the conjunctiva, conjunctivitis, scleroconjunctivitis, isolated scleritis, episcleritis, and interstitial keratitis. Cataract, which is mostly a complication of prolonged uveitis and subluxation of the lens, can occur. Glaucoma, secondary to syphilitic iridocyclitis can also occur. Granulomatous or nongranulomatous uveitis is an important manifestation of ocular syphilis. Dilated iris capillaries and various patterns of iris atrophy have been reported [320, 322–325]. Pupillary abnormalities include Argyl Robertson pupil with irregular miotic pupil and light near dissociation [326]. Rarely syphilitic lesions of the skin may involve the eyelids in the form of a chancre or condylomata lata [327].

Posterior segment manifestations of acquired syphilitic chorioretinitis include vasculitis causing arteriole and venous occlusive vascular phenomenon [328]. Involvement of the macula may occur in the form of macular edema, stellate maculopathy in neuroretinitis, subretinal neovascular membrane, and disciform macular scarring. Also macular pseudohypopyon presenting with serous retinal detachment with an exudative fluid meniscus has been reported [329–332]. Retinal and choroidal detachment has been reported. Rarely, the big blind spot syndrome has been reported [333]. This syndrome is described in syphilitic optic perineuritis that is characterized by optic disc swelling with normal intracranial pressure, normal vision, and normal pupils. Enlargement of the blind spot may be the presenting feature.

Acute syphilitic posterior placoid chorioretinitis, a syndrome characterized by large yellow placoid macular lesions with subsequent visual loss, has been reported in secondary syphilis [334]. Vitritis is a late manifestation of syphilis. HIV positive patients with syphilis may present with dense vitritis as their initial manifestation of HIV [335].

16.5.1.4  Diagnosis

Demonstration of T. palladium is the primary test early in the disease, before seroconversion, and when no active lesions are present. The techniques of demonstration include dark field microscopy, fluorescent microscopy [336], and cultures where viable T. palladium can be maintained in specific tissue cultures.

There is no ideal serological test, and the choice of serological test will depend on the sensitivity and specificity of the test at the various stages of the disease [337]. Serological tests for syphilis are divided into two main categories, nontreponema tests and treponema tests. The nontreponema tests detect antibodies against cardiolipin-lecithin-cholesterol antigens. The most commonly used nontreponema tests include the venereal disease research laboratory (VDRL) and rapid plasma reagin (RPR). Treponema tests detect antibodies against treponema antigens [338] and include fluorescent treponema antibody absorption test (FTA-abs), the hemagglutination treponema test for syphilis (HATTS), and the microhemagglutination test.

Although no specific test can make the diagnosis of neurosyphilis in all patients, the most useful laboratory test is examination of cerebrospinal fluid obtained with lumbar puncture where the common findings are detection of leucocytosis (> than 5 WBC/ micro L), mild monocular pleocytosis (10–400 cells/ micro L), elevated proteins (0.46–2.0 g/L) and antibodies by VDRL.

The diagnosis of congenital syphilis is difficult to confirm in infants because of the relative lack of symptoms and the initial seronegativity of the tests [318]. When the results of the nontreponema and treponema tests are higher in the infant than the mother, this strongly suggests congenital disease. Demonstration of T. palladium can be revealed by scraping fresh lesions.

16.5.1.5  Syphilis and AIDS

Recent increases in the number of reported cases of syphilis coincide with the AIDS pandemic [309]. Risk factors for both syphilis and HIV are similar, thus it is important to test for both syphilis and HIV in patients who test positive for either agent [339]. Concurrent HIV infection tends to modify the course of syphilis