The rubella virus is the prototypical teratogenic viral agent. It consists of single-stranded RNA surrounded by a lipid envelope, or “toga,” hence its inclusion in the Togaviridae family. Although rubella remains an important cause of blindness in resource-limited regions and nations, the epidemic pattern of the disease was interrupted in the United States by introduction of the rubella vaccine in 1969. The peak age incidence shifted from 5–9 years (young children) in the prevaccine era to 15–19 years (older children) and more recently to 20–24 years (young adults). Approximately 5%–25% of women of childbearing age are susceptible to primary infection. Rubella may involve the retina as part of the congenital rubella syndrome (CRS) or during acquired infection (German measles).
The fetus is infected with the rubella virus transplacentally, secondary to maternal viremia during the course of primary infection. The frequency of fetal infection is highest during the first 10 weeks and the final month of pregnancy, with the rate of congenital defects varying inversely with gestational age. Although obvious maternal infection during the first trimester of pregnancy may end in spontaneous abortion, stillbirth, or severe fetal malformations, seropositive asymptomatic maternal rubella may also result in severe fetal disease.
The classic features of CRS include cardiac malformations (patent ductus arteriosus, interventricular septal defects, and pulmonic stenosis), ocular findings (chorioretinitis, cataract, corneal clouding, microphthalmia, strabismus, and glaucoma), and deafness (Fig 11-12). Hearing loss is the most common systemic finding. Individuals with CRS are at greater risk for diabetes mellitus and subsequent diabetic retinopathy later in life.
A unilateral or bilateral pigmentary retinopathy is the most common ocular manifestation of CRS (25%–50%), followed by cataract (15%) and glaucoma (10%). The pigmentary disturbance, often described as “salt-and-pepper” fundus, shows considerable variation, ranging from finely stippled, bone spicule–like, small, black, irregular masses to gross pigmentary irregularities with coarse, blotchy mottling (Fig 11-13). It can be stationary or progressive. Despite loss of the foveal light reflex and prominent pigmentary changes, neither vision nor electroretinogram results are typically affected. Congenital (nuclear) cataracts and microphthalmia are the most frequent causes of poor visual acuity and, rarely, CNV. Unless otherwise compromised by glaucoma, the optic nerve and the retinal vessels are typically normal in appearance.
Figure 11-12 Patient with congenital rubella syndrome who exhibited cataract, esotropia, cognitive impairment, congenital heart disease, and deafness.
(Courtesy of John D. Sheppard Jr, MD.)
Figure 11-13 Fundus photograph of congenital rubella syndrome with diffuse retinal pigment epithelial mottling showing “salt-and-pepper” appearance.
(Courtesy of Albert T. Vitale, MD.)
Histologic studies of the lens reveal retained cell nuclei in the embryonic nucleus as well as anterior and posterior cortical degeneration. Poor development of the pupil dilator muscle, necrosis of the iris pigment epithelium, and chronic nongranulomatous inflammation may be present in the iris. The RPE displays alternating areas of atrophy and hypertrophy. The anterior chamber angle appears similar to that of congenital glaucoma. Although the mechanism of rubella embryopathy is not known at the cellular level, it is thought that the virus inhibits cellular multiplication and establishes a chronic, persistent infection during organogenesis. The persistence of viral replication after birth, with ongoing tissue damage, is central to the pathogenesis of CRS and may explain the appearance of hearing and neurologic and/or ocular deficits long after birth.
The pigmentary retinal changes and associated systemic findings, together with a history of maternal exposure to rubella, suggest the diagnosis of CRS. Serologic criteria for rubella infection include a fourfold increase in rubella-specific immunoglobulin G (IgG) in paired sera 1–2 weeks apart or the new appearance of rubella-specific IgM. Because the fetus is capable of mounting an immune response to the rubella virus, specific IgM or IgA antibodies to rubella in the cord blood confirm the diagnosis.
The differential diagnosis of congenital rubella retinitis consists of entities constituting the TORCH (toxoplasmosis, other agents, rubella, cytomegalovirus, and herpesviruses) syndrome. See also BCSC Section 6, Pediatric Ophthalmology and Strabismus, for additional discussion of congenital rubella. Other viral illnesses, such as mumps, roseola subitum, and postvaccination encephalitis, should be considered and ruled out by appropriate serologic tests. There is no specific antiviral therapy for congenital rubella, and treatment is supportive.
Acquired infection (German measles) presents with a prodrome of malaise and fever in adolescents and adults before onset of the rubella exanthem. An erythematous, maculopapular rash appears first on the face, spreads toward the hands and feet, involves the entire body within 24 hours, and disappears by the third day. Although the rash is not always prominent and the occurrence of fever is variable, lymphadenopathy is invariably present.
The most frequent ocular complication of postnatally acquired rubella is conjunctivitis (70%), followed by the infrequent occurrence of epithelial keratitis and retinitis. Acquired rubella retinitis has been described in adults presenting with acute-onset decreased vision and multifocal chorioretinitis, with large areas of bullous neurosensory detachment, underlying pigment epithelial detachment involving the entire posterior pole, anterior chamber and preretinal vitreous cells, dark gray atrophic lesions of the RPE, normal appearance of the retinal vessels and optic nerve, and absence of retinal hemorrhage. The neurosensory detachments resolve spontaneously, and visual acuity returns to normal. Chronic rubella virus infection has been implicated in the pathogenesis of FUS, as evidenced by the presence of rubella-specific intraocular antibody production and the intraocular persistence of the virus (for more detailed discussion of FUS, see Chapter 8).
Uncomplicated acquired rubella does not require specific therapy; however, rubella retinitis and postvaccination optic neuritis may respond well to systemic corticosteroids.
Arnold JJ, McIntosh ED, Martin FJ, Menser MA. A fifty-year follow-up of ocular defects in congenital rubella: late ocular manifestations. Aust N Z J Ophthalmol. 1994;22(1):1–6.
Givens KT, Lee DA, Jones T, Ilstrup DM. Congenital rubella syndrome: ophthalmic manifestations and associated systemic disorders. Br J Ophthalmol. 1993;77(6):358–363.
Quentin CD, Reiber H. Fuchs heterochromic cyclitis: rubella virus antibodies and genome in aqueous humor. Am J Ophthalmol. 2004;138(1):46–54.
Excerpted from BCSC 2020-2021 series: Section 9 - Uveitis and Ocular Inflammation. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.