Figure 28-15 Wyburn-Mason syndrome, or racemose angioma of the retina, left eye.
Klippel-Trénaunay-Weber Syndrome
Klippel-Trénaunay syndrome (KTS) is a neurocutaneous disorder consisting of a vascular nevus involving an extremity, varicosities of that extremity, and hypertrophy of bone and soft tissue. When arteriovenous malformation is also present, the disease is called Klippel-Trénaunay-Weber syndrome (KTWS). Occurrence of KTWS is sporadic, the etiology is unknown, and there is no established incidence. Ophthalmic findings include vascular anomalies of the orbit, iris, retina, choroid, and optic nerve, as well as optic nerve and chiasmal gliomas. KTS is a complex syndrome with no single treatment protocol. Treatment is individualized to the patient. At present, many of the symptoms may be treated, but there is no cure for this syndrome.
Bothun ED, Kao T, Guo Y, Christiansen SP. Bilateral optic nerve drusen and gliomas in Klippel-Trénaunay syndrome. J AAPOS. 2011;15(1):77–79.
Intrauterine or Perinatal Infection
Maternally transmitted congenital infections cause ocular damage in 3 ways:
through direct action of the infecting agent, which damages tissue through a teratogenic effect, which causes malformation
through a delayed reactivation of the agent after birth that damages developed tissue by direct action or inflammation
These infections can cause ongoing tissue damage; long-term evaluation is thus required in order to determine their full impact. Most perinatal disorders have an exceedingly broad spectrum of clinical presentation, ranging from silent disease to life-threatening tissue and organ damage. The common types of congenital infections can be remembered by the acronym TORCH: toxoplasmosis; rubella; cytomegalovirus; and herpesviruses. Other infections discussed in this section include syphilis and lymphocytic choriomeningitis virus.
Toxoplasmosis
The etiologic agent of toxoplasmosis, Toxoplasma gondii, is an obligate intracellular parasite. Cats are the definitive host, wherein the parasite resides in the intestinal mucosa in the form of an oocyst. Once excreted into the environment, the oocyst can be ingested by many animals, including humans. Humans can also acquire the disease secondarily by ingesting undercooked infected meat or contaminated drinking water. The ingested cyst has a predilection for muscle, including the heart, and neural tissue, including the retina. Encysted organisms can remain dormant indefinitely, or the cyst can rupture, releasing hundreds of thousands of tachyzoites, the proliferative phase of the protozoan. The stimulus for local reactivation of an infected cyst is unknown.
Systemic infection in humans is common and usually goes undiagnosed. Symptoms may include fever, lymphadenopathy, and sore throat. The percentage of antibody titer–positive persons in the United States increases with age (<5 years of age, 5%; >80 years of age, 60%).
The incidence of congenital toxoplasmosis ranges from 1 to 10 per 10,000 live births. Toxoplasmosis can be acquired congenitally via transplacental transmission from an infected mother to the fetus. Congenital infection can result in retinitis, hepatosplenomegaly, intracranial calcifications, microcephaly, and developmental delay.
Ocular manifestations besides retinitis include choroiditis, iritis, and anterior uveitis (Fig 28-16). The active area of retinal inflammation is usually thickened and cream colored with an overlying vitritis, frequently in the macular area. This area may be at the edge of an old, flat, atrophic scar (a so-called satellite lesion). Previously, apparently acquired Toxoplasma retinitis was thought to represent reactivation of a congenital infection; however, recent evidence suggests that most of these patients are infected postnatally.
Figure 28-16 Toxoplasmosis chorioretinitis, right eye.
The diagnosis of toxoplasmosis is primarily clinical and is based on the characteristic retinal lesions. It can be supported by a positive enzyme-linked immunosorbent assay (ELISA) for Toxoplasma gondii antibody. Lack of antibody essentially rules out the diagnosis. Because maternal immunoglobulin M (IgM) does not cross the placenta, the presence of Toxoplasma-specific IgM in the infant serum is diagnostic of congenital infection.
Ocular inflammation from reactivated toxoplasmosis does not require treatment unless it threatens vision. Vision can be compromised by the location of the reactivation adjacent to the macula or optic nerve or by significant vitritis. Systemic treatment involves the use of 1 or more antimicrobial drugs with or without oral corticosteroids. The most commonly used antimicrobial agents are pyrimethamine and sulfadiazine. Steroids should never be used without antimicrobial coverage. Intravitreal injection of clindamycin and dexamethasone has been reported as a possible alternative treatment.
In the setting of congenital Toxoplasma infection, prenatal treatment and treatment during the
infant’s first year of life appear to decrease the risk of poor visual outcomes. In congenitally infected children, new lesions may occur in the second decade of life; serial monitoring of these patients is thus necessary. For additional details on drug therapy for toxoplasmosis, see BCSC Section 9,
Intraocular Inflammation and Uveitis.
Soheilian M, Ramezani A, Azimzadeh A, et al. Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisone in treatment of ocular toxoplasmosis. Ophthalmology. 2011;118(1):134–141.
Rubella
Congenital rubella (German measles) syndrome is a well-defined combination of ocular, otologic, and cardiac abnormalities, accompanied by microcephaly and variable developmental delay. Described in 1941 by the ophthalmologist Sir Norman Gregg, the rubella virus was the first virus recognized as a teratogenic agent. The syndrome is caused by transplacental transmission of the rubella virus from an infected mother to the fetus. The incidence has decreased markedly in North America since widespread vaccination of children was instituted in the late 1960s, although rubella remains a cause of infant morbidity and mortality in less-developed countries.
Ocular abnormalities found in congenital rubella syndrome include a peculiar nuclear cataract that is sometimes floating in a liquefied lens cortex, glaucoma, microphthalmos, and retinal abnormalities that vary from a subtle salt-and-pepper retinopathy (most common finding; Fig 28-17) to pseudoretinitis pigmentosa. Diagnosis is based on this characteristic clinical picture and is supported by serologic testing. The virus itself can be isolated from pharyngeal swabs and from the lens contents at the time of cataract surgery.
Figure 28-17 Fundus photograph of a 6-year-old patient with rubella syndrome (electroretinogram results normal).
Lensectomy is usually required for cataracts. Infected eyes are prone to postoperative inflammation and subsequent secondary membrane formation. Topical steroids and mydriatics should be used aggressively. In adults, rubella virus infection has been identified as a probable cause of Fuchs heterochromic iridocyclitis.
Cytomegalovirus
Cytomegalovirus (CMV), a member of the herpesvirus family, is a ubiquitous virus that can cause a wide range of infection, from asymptomatic acquired infection in immunocompetent individuals to severe infections in newborn infants and immunocompromised patients. Over 80% of adults in developed countries have antibodies to the virus.
Congenital infection with CMV is the most common congenital infection in humans; it occurs in approximately 1% of infants. Clinically apparent disease is present in 10%–15% of infected neonates, and 20%–30% of these cases are fatal. Transmission to the fetus or newborn can occur transplacentally, from contact with an infected birth canal during delivery, or from ingestion of infected breast milk or maternal secretions. Congenital CMV disease is characterized by fever, jaundice, hematologic abnormalities, deafness, microcephaly, and periventricular calcifications.
Ophthalmic manifestations of congenital CMV infection occur primarily in infants with systemic