More Evidence Links Rubella to Eye Inflammation

CHICAGO, Sept. 21 -- Rubella vaccination reduces the risk of Fuchs heterochromic iridocyclitis (FHI), investigators here reported, providing additional support for a link between rubella virus infection and inflammation.

Over a 20-year period coinciding with increased rates of rubella vaccination, the proportion of iridocyclitis cases attributable to FHI declined significantly, whereas rates of two other types of inflammation of the iris and ciliary body did not, Debra Goldstein, M.D., of the University of Illinois at Chicago, and colleagues, reported in the American Journal of Ophthalmology.

"We believe that the data provide convincing epidemiologic support and plausibility to earlier research implicating the rubella virus as a cause of FHI," the researchers concluded.

An intraocular inflammatory disease, FHI accounts for 2% to 11% of all cases of anterior uveitis. Anti-inflammatory therapy does not change the course the disease, so patients are monitored and treated as complications such as cataracts and glaucoma arise.

Two recent studies suggested a causal relationship between ocular infection with rubella virus and FHI. One of the studies provided especially compelling evidence, as 100% of patients with diagnosed FHI had intraocular synthesis of rubella antibodies (Am J Ophthalmol 2004;138:46-54).

The second study demonstrated intraocular rubella antibody production in 13 of 14 patients with FHI versus none of 32 patients with non-FHI ocular inflammatory disease (Am J Ophthalmol 2006;141:212-214).

Continuing the investigation of the rubella-FHI link, Dr. Goldstein and colleagues reviewed records on 3,856 patients seen at the University of Illinois uveitis service from 1985 through 2005.

Overall, FHI accounted for 3.40% of the patients, idiopathic chronic iridocyclitis for 7.47%, and idiopathic chronic granulomatous iridocyclitis for 4.36%.

Among patients born from 1919 through 1958, the rate of FHI varied from 3.51% to 5.19% and the rate of idiopathic chronic granulomatous iridocyclitis from 3.51% to 4.72%. Idiopathic chronic iridocyclitis demonstrated more variability (6.63% to 11.32%).

For patients born from 1959 through 1968, the percentage of uveitis patients with FHI decreased 4.58% to 2.97%, representing a decline of 64.8%. FHI as a percent of the total decreased by an additional 39.7% (to 1.18%) in patients born from 1969 through 1978.

Among patients born from 1989 through 1998, FHI accounted for a single case of uveitis.

"These precipitous declines were not seen in patients diagnosed with idiopathic chronic iridocyclitis or idiopathic chronic granulomatous iridocyclitis," the authors reported.

Trend analysis showed that the distribution of FHI over time differed significantly from idiopathic chronic iridocyclitis (P=0.0007) and from idiopathic chronic granulomatous iridocyclitis (P=0.0002). In contrast, trends in rates of the two idiopathic forms of iridocyclitis did not differ from each other.

Another finding that supported the FHI-rubella link related to the proportion of foreign-born patients with FHI. From 1949 to 1988 the percentage of FHI patients born outside the United States increased steadily, whereas the percentage of foreign-born patients with the two idiopathic forms of iridocyclitis never exceeded 40%.

The authors noted that the percentage of foreign-born patients with FHI increased in parallel with the proportion of foreign-born patients with rubella. Moreover, most of the countries represented by patients in the study did not institute rubella vaccination programs until the 1980s or later.

"The similarities between congenital rubella syndrome and FHI in the United Stages, both in terms of the overall decline and the increase in proportion of disease in foreign-born individuals suggests that the FHI data may, in fact, apply to a larger population," the authors concluded.

In an editorial that accompanied the article, Aniki Rothova, M.D., of University Medical Center Utrecht in the Netherlands, said, "It is convincing that rubella virus initiates-at least in some of the patients-the development of [FHI]."

However, Dr. Rothova continued, multiple issues related to the disease remain unresolved: the potential for other initiating factors; the association between uveitis and cataract; the absence of similar signs and symptoms in other intraocular inflammations; and the identity of the antigen at the center of the inflammatory process.

The authors noted several limitations of the study.

"We assumed that the subjects born in the United States after 1957, particularly those born after 1969, received the rubella vaccine and developed immunity to future infection."

"A second limitation involved the acquisition of data. Because this was a retrospective study, we were not able to ascertain the country of origin of 100% of the patients."