Uveitis Crash Course
A primer on the prevalence and epidemiology of uveitis.
Uveitis, or inflammation of the uvea, is responsible for between 10% and 15% of all cases of blindness and for 30,000 new cases of legal blindness annually in the United States.1,2 In up to 50% of cases, there is an underlying systemic disease,3 and the practicing retina specialist should understand the presentation patterns and implications these diseases can have for patients. In this article, we review recent findings regarding the incidence, prevalence, and associations of this vision-threatening, multifarious disease.
AT A GLANCE
• Uveitis is generally more common in women and boys, and the prevalence of disease increases with age.
• Anterior uveitis is more common than posterior uveitis or panuveitis, and intermediate uveitis is rare.
• Noninfectious uveitis is much more common than infectious uveitis.
INCIDENCE AND PREVALENCE
The overall incidence and prevalence of uveitis varies greatly among regions of the United States. A study in the 1960s reported an incidence of 17.4 new cases of uveitis per 100,000 persons per year.2 However, more recent regional studies suggest that this may have been an underestimate. The true incidence of uveitis may be as high as 24.9 new cases per 100,000 persons per year in Hawaii and the Pacific Islands, 25.6 in the Pacific Northwest, and as many as 52.4 in Northern California.4-6
Another study recently demonstrated a prevalence of 31 cases per 100,000 person-years for children under age 18 years, 133 for adults aged 18-64 years, and 220 for those 65 years and older in the United States.7 In the pediatric population, boys tended to be diagnosed with uveitis more than girls (55%; 34 vs. 29 cases per 100,000 person-years), and women were more likely to have uveitis than men (57%; 146 vs. 119 cases per 100,000 person-years). In 2015, there were roughly 328,019 cases of uveitis in the US adult population and 23,152 cases in the US pediatric population.7
Uveitis is classified according to anatomic location: anterior, intermediate, posterior, or panuveitis.8 Anterior uveitis is the most common, accounting for between 30% and 90% of cases.9,10 Posterior uveitis is the second most common form, accounting for 4.7% to 30% of cases. Intermediate uveitis accounts for 1.4% to 12.2% of cases, and more than 60% of these cases are idiopathic.2,9 Panuveitis accounts for 1.4% to 9.4% of cases.11
In US adults and children, 91% and 95% of cases, respectively, are noninfectious.7 Of adult noninfectious causes, only 9% can be attributed to a systemic immunologic condition.9 With the exception of syphilis, in general, infectious causes of uveitis are decreasing in the United States.11,12
Sarcoidosis, a disease in which abnormal collections of inflammatory cells form granulomas, accounts for approximately 1% to 3% of pediatric uveitis cases and 10% of adult uveitis cases and can present in many ways.13 In the southeastern United States, sarcoidosis accounts for 25% of uveitis in black patients, who are more likely to have ocular involvement than whites.14 Age of presentation is bimodal, with the incidence typically peaking in the third and sixth decades of life.13 Ocular sarcoidosis most commonly presents bilaterally, and 90% of cases are chronic in nature, with a highly variable anatomic location of inflammation. A study of 112 eyes with sarcoid uveitis found that only 81% of cases presented in a classic granulomatous pattern. Due to these variable presentations, sarcoidosis should be included in the differential diagnosis of any patient with uveitis.
Toxoplasmosis is the most common form of posterior uveitis in the United States, accounting for between 2.8% and 10% of cases.2,4,7,10,11,15 Current epidemiologic studies show a lower rate than previous studies, and a recent study found a 78% decline in prevalence of ocular toxoplasmosis in the period from 2008 to 2012, compared with the period between 1973 and 1977.12 The disease burden is anywhere from 2150 to 7500 cases each year.12 Toxoplasmosis most commonly presents as a retinochoroiditis with overlying vitritis, and it is more common among Hispanic individuals in the United States.12
Snapshot of Uveitis
The number of cases of syphilis in the United States has climbed since 2000, with an increase in regional outbreaks of ocular syphilis since 2015.16 Although ocular syphilis is rare, it is a treatable form of inflammation. It is estimated that syphilis accounts for 1.29% of all uveitis cases, and, of all patients diagnosed with syphilis, 0.46% to 0.6% are also diagnosed with uveitis, for an overall incidence in the United States of roughly four cases per million patients.17 In general, patients tend to be younger men of a nonwhite ethnic group. Given the potential for syphilis to masquerade in many ways, it is important to test any patient presenting with uveitis for syphilis.
ARN and CMV
Acute retinal necrosis (ARN) and cytomegalovirus (CMV) retinitis are uncommon but potentially devastating forms of uveitis. ARN has an estimated minimum incidence of 0.5 to 0.63 new cases per million population and is caused by the human herpes family of viruses, most commonly herpes simplex 1 and 2, and by varicella zoster virus.18,19 Cases are unilateral in 84.4% to 90.3% of patients and bilateral in 9.7% to 15.6% of patients, with bilateral cases presenting either simultaneously or within 3 months of each other, with no age or sex predilection.18,19
ARN often occurs in immunocompetent patients, with only 22.5% to 28.9% of cases in immunocompromised individuals.18,19 CMV retinitis primarily affects immunocompromised individuals, especially those with human immunodeficiency virus.20 Advances in antiretroviral therapy (ART) have led to a decrease in CMV retinitis from 14.8 per 100 person-years in the pre-ART era to 0.4 per 100 person-years in the modern era.20 Overall visual outcome in most patients at 6 months is worse than 20/200.18-20
A DISEASE WITH SERIOUS CONSEQUENCES
Vision loss from uveitis can vary based on the location of the inflammation. A 25% loss of visual acuity occurs in 1% to 4% of patients with anterior uveitis, 43% of patients with posterior uveitis, 66% of patients with intermediate uveitis, and 40% of patients with panuveitis.21,22 Other studies have indicated that up to 35% of patients with uveitis have visual impairment or blindness, with cystoid macular edema as the leading cause of vision loss followed by cataract formation and glaucoma.3,23
Given that multiple other conditions have similar presentations, it is important for retina specialists to perform a differential diagnosis of all patients with uveitis so that treatment, if necessary, can be initiated as early as possible.
1. Nussenblatt RB. The natural history of uveitis. Int Ophthalmol. 1990;14(5-6):303-308.
2. Darrell RW, Wagener HP, Kurland LT. Epidemiology of uveitis. Incidence and prevalence in a small urban community. Arch Ophthalmol. 1962;68:502-514.
3. Suttorp-Schulten MSA, Rothova A. The possible impact of uveitis in blindness: a literature survey. Br J Ophthalmol. 1996;80(9):844-848.
4. Acharya NR, Tham VM, Esterberg E, et al. Incidence and prevalence of uveitis: results from the Pacific Ocular Inflammation Study. JAMA Ophthalmol. 2013;131(11):1405-1412.
5. Suhler EB, Lloyd MJ, Choi D, et al. Incidence and prevalence of uveitis in veterans affairs medical centers of the Pacific Northwest. Am J Ophthalmol. 2008;146(6):890-896.
6. Gritz DC, Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study. Ophthalmology. 2004;111(3):491-500.
7. Thorne JE, Suhler EB, Skup M, et al. Prevalence of noninfectious uveitis in the United States: a claims-based analysis. JAMA Ophthalmol. 2016;134(11)1237-1245.
8. Jabs DA, Nussenblatt RB, Rosenbaum JT; for the Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005;140(3):509-516.
9. McCannel CA, Holland GN, Helm CJ, Cornell PJ, Winston JV, Rimmer TG. Causes of uveitis in the general practice of ophthalmology. UCLA Community-Based Uveitis Study Group. Am J Ophthalmol. 1996;121(1):35-46.
10. Rodriguez A, Calonge M, Pedroza-Seres M, et al. Referral patterns of uveitis in a tertiary eye care center. Arch Ophthalmol. 1996;114(5):593-599.
11. Tsirouki T, Dastiridou A, Symeonidis C, et al. A focus on the epidemiology of Uuveitis. Ocul Immunol Inflamm. 2016;1-15.
12. Hou JH, Patel SS, Farooq AV, Qadir AA, Tessler HH, Goldstein DA. Decline in ocular toxoplasmosis over 40 years at a tertiary referral practice in the United States [published online ahead of print November 28, 2016]. Ocul Immunol Inflamm.
13. Pasadhika S, Rosenbaum JT. Ocular sarcoidosis. Clin Chest Med. 2015;36(4):669-683.
14. Merrill PT, Kim J, Cox TA, Betor CC, McCallum RM, Jaffe GJ. Uveitis in the southeastern United States. Curr Eye Res. 1997;16(9):865-874.
15. Engelhard SB, Patel V, Reddy AK. Intermediate uveitis, posterior uveitis, and panuveitis in the Mid-Atlantic USA. Clin Ophthalmol. 2015;9:1549-1555.
16. Oliver SE, Auin M, Atwell L, et al. Ocular syphilis – Eight jurisdictions, United States, 2014-2015. MMWR Morb Mortal Wkly Rep. 2016;65(43):1185-1188.
17. Albini T, Callaway NF, Pershing S, Wang SK, Moshfeghi AA, Moshfeghi DM. Trends in hospitalization and incidence rate for syphilitic uveitis in the United States from 1998 to 2009. Am J Ophthalmol. 2017;180:133-141.
18. Cochrane TF, Silvestri G, McDowell C, et al. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study. Eye (Lond). 2012;26(3):370-377.
19. Muthiah MN, Michaelids M, Child CS, Mitchll SM. Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK. Br J Ophthalmol. 2007;91(11):1452-1455.
20. Port AD, Orlin A, Kiss S, Patel S, D’Amico DJ, Gupta MP. Cytomegalovirus retinitis: a review. J Ocul Pharmacol Ther. 2017;33(4):224-234.
21. Couto C, Merlo TIL. Epidemiological study of patients with uveitis in Buenos Aires, Argentina. In: Dernouchamps JP, Verougstraete C, Caspers-Velu L, Tassignon MJ, eds. Recent advances in uveitis. New York: Kugler Publications,; 1993:171-174.
22. Linssen A, Meenken C. Outcomes of HLA-B-27-positive and HLA-B27-negative acute anterior uveitis. Am J Ophthalmol. 1995;120(3):351-361.
23. Rothova A, Suttorp-van Schulten MSA, Treffers WE, Kijlstra A. Causes and frequency of blindness in patients with intraocular inflammatory disease. Br J Ophthalmol. 1996;80(4):332-336.
Eric L. Crowell, MD, MPH
• assistant of ophthalmology, advanced subspecialty training program, division of ocular immunology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, in Baltimore, Md.
• financial interest: none acknowledged
Ashvini K. Reddy, MD
• assistant professor of ophthalmology in the division of ocular immunology at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, in Baltimore, Md.
• financial interest: none acknowledged