These results indicate that the risk of relapse for cases of remitted primary anterior uveitis among patients presenting to tertiary uveitis centers is high, with an estimated rate of relapse of inflammation of 39% at 1.5 years after remission based on this sample. The Kaplan-Meier curve describing the experience of our patients suggests that the risk of first relapse may diminish among patients still free of relapse after two years (see ), but that even after two years the risk of relapse is not negligible. Given that many patients will experience a uveitis relapse, management of patients with primary anterior uveitis should include a plan as to how relapses will be detected so as to allow prompt treatment. Ophthalmologists cannot see all patients frequently enough to promptly detect all relapses at scheduled exams, and clinical experience suggests that sequelae of uveitis can be avoided in most cases with prompt diagnosis and treatment of relapses. Therefore, patients should be told that the risk of recurrence is high and should be instructed regarding the signs and symptoms of uveitis so that they can recognize relapses and promptly report for care. Patients with fewer symptoms associated with anterior uveitis activity may need to be seen for planned follow-up visits more frequently than patients with easily detectable symptoms.
Prior reports have shown that the mean age of onset of acute anterior uveitis is in the 30’s.16–17
Our analysis suggests that recurrence risk varies by age—a first episode of anterior uveitis in younger adults is more likely to recur. It is not uncommon for more severe cases of a disease to present earlier in life than less severe cases, which may explain this observation. Smoking, which has been observed to increase the risk of relapse of ocular inflammation in general 18–19
, was not observed to increase relapse risk specifically in primary anterior uveitis cases.
Spondyloarthropathy and HLA-B27 positive status are well-known to be risk factors for anterior uveitis. 7, 20–21
Prior reports on the risk of recurrence of anterior uveitis have included a mixture of primary and already recurrent uveitis cases; the latter group can be expected to have a higher relapse risk than the former, given that not all primary anterior uveitis cases will relapse. Several studies of such mixed groups of patients have reported a high frequency of recurrence of anterior uveitis in HLA-B27 positive patients with a mean number of attacks ranging from 0.6–3.3 attacks per patient per year of follow up.7, 16, 17, 22, 23
Among studies comparing relapse risk between HLA-B27 positive and negative individuals, one study (performed at a tertiary uveitis center participating in the present study) found a higher frequency of relapses in HLA-B27 positive patients as compared with HLA-B27 negative patients,6
while another study found an equal number of recurrences per eye in HLA-B27 positive and negative patients.16
In our study, HLA-B27 positive status and spondyloarthropathy were not associated with higher risk of relapse, supporting the second result. However, given the available statistical precision our results do not rule out a moderately increased relapse risk in these groups. Although the participating clinics have pursued systemic inflammatory disease diagnoses aggressively throughout their history, it is possible that milder cases of spondyloarthropathy may not have been ascertained in every instance; if spondyloarthropathy in fact is associated with a higher risk of relapse, failure to ascertain these cases may have biased the association toward the null. Our results do not address the frequency of relapse among cases with an established recurrent acute anterior uveitis pattern, which the studies previously cited suggest may be higher among HLA-B27 positive individuals, especially those with both HLA-B27 and a spondyloarthropathy.6, 7, 17
Other systemic disease diagnoses were infrequent among our patients with primary anterior uveitis, limiting our ability to comment on the possible impact of such conditions on relapse risk. Based on the imprecise estimates available, primary anterior uveitis cases associated with sarcoidosis tended to have a higher estimated relapse risk; this preliminary observation requires confirmation in additional studies as the association was non-significant and could well be due to random error.
The strengths of this study included its derivation from a very large parent cohort, which allowed us to look at a relatively large number of primary anterior uveitis cases followed from remission of their index inflammatory event, and the use of quality control efforts to optimize the quality of retrospective data collection. Limitations derive primarily from the retrospective nature of the study. Incomplete follow-up may have led to a mis-estimation of the recurrence rate if patients who did not return for follow-up had a different relapse risk than those who did; if subjects with no recurrences were less likely to return for follow up visits, our overall relapse rate would be overestimated, but still would be high. Relapse was not always identified in the context of scheduled follow-up visits, rather patients were instructed to return for follow up sooner than scheduled visits if they had symptoms of a recurrence. Given that subjects were seen at tertiary centers, cases may have been especially severe and perhaps therefore more prone to relapse, which also would lead to an overestimate of the recurrence rate with respect to a non-tertiary care practice, but which would be representative of tertiary uveitis practices. This problem may be partially mitigated by the exclusion of patients presenting more than 90 days after initial diagnosis, as most patients presenting soon after initial diagnosis are likely to have received their primary eye care at our institutional facilities. In addition, the number of subjects with each of the different systemic inflammatory conditions was relatively small despite the multicenter approach, leading to imprecise estimates of the risk of relapse for these conditions. If systemic conditions were under-diagnosed despite our best efforts—and in truth lead to higher or lower relapse risk—risk ratios associated with these conditions would tend to be biased toward no association, meaning that increases or decreases in risk with these conditions could have been missed by this study. However, none of these limitations are likely to have introduced enough bias so as to affect the primary conclusions that the risk of relapse of primary anterior uveitis is high, and that relapses occur more frequently in younger persons than in adults ages 35 years and higher.
In summary, among cases of primary anterior uveitis presenting to tertiary uveitis centers within 90 days of initial diagnosis and achieving an initial medication-free remission of inflammation within the first 90 days that lasted for at least another 90 days, relapse of uveitis was frequent, occurring in 39% within 1.5 years. Age in the young adult range was associated with an increased relapse risk. Management of these patients should include an explicit plan for detecting relapses—usually based on counseling patients how to respond to new symptoms suggesting uveitis relapse, given that for most cases relapses will be highly symptomatic. However, patients at high risk of relapse for whom obvious uveitic symptoms were not a prominent part of initial presentation may require close monitoring for signs of relapse, particularly in the first two years following presentation of uveitis.