HIGHLIGHTS
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Uveitis incidence is higher than previously reported in the literature.
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Rising uveitis incidence, with disruptions noted during the COVID-19 pandemic.
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Increased prevalence of low vision and blindness in the uveitis cohort.
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Sarcoidosis and spondyloarthropathy are common systemic associations with uveitis.
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Prednisone is the most used treatment, followed by methotrexate and adalimumab.
Objective
To analyze the demographics, immunosuppressant use, associated systemic diseases, ocular comorbidities, and incidence and prevalence of uveitis and associated low vision using the United States TriNetX database from 2013-2023.
Design
Retrospective cross-sectional and trend study.
Participants
Subjects with uveitis in the TriNetX database.
Methods
Subjects with uveitis were identified with International Classification for Disease codes and then divided into anatomic subtypes based on the diagnosis. Incidence and prevalence data were collected from 2013-2023. Additional data collected included demographics, use of systemic immunosuppressive medications, presence of an associated systemic disease, and associated ocular complications.
Main Outcome Measures
The primary outcomes were the incidence and prevalence of uveitis (annual and cumulative) with additional analysis by anatomic subtype. Secondary outcomes were the incidence and prevalence of low vision (annual and cumulative).
Results
Out of the 109,026,851 subjects in the database, 278,333 (0.26%) had a diagnosis of uveitis. The mean age was 56 years (Standard Deviation = 21, 95% Confidence Interval (CI) 55.9-56.1), and the majority were female (n = 149,186; 53.6%, 95% CI 53.4%-53.8%) and white (n = 150,578; 54.1%, 95% CI 53.9%-54.3%). Anterior uveitis was the most common subtype (n = 209,073, 75.1%). Oral prednisone (n = 62,834; 22.6%, 95% CI 22.5%-22.8%) was the most used immunosuppressant and methotrexate (n = 15,817; 5.7%, 95% CI 5.6%-5.8%) was the most prevalent corticosteroid-sparing immunosuppressive agent. Inflammatory spondyloarthropathies (n = 18,372; 6.6%, 95% CI 6.5%-6.7%) were the most frequently associated systemic disease. The cumulative incidence and prevalence of uveitis from 2013-2023 were 212.5 and 260.8 per 100,000 persons, respectively.
Conclusions
This study represents one of the largest uveitis populations analyzed in the United States, revealing a rising incidence of all uveitis subtypes and an increase in low vision among affected patients over the past decade in the database. Prospective studies are needed to identify the factors driving these trends and to develop strategies to prevent vision loss and ocular complications in uveitis patients.
T he uveitides represent a diverse group of diseases characterized by intraocular inflammation, which can lead to sight-threatening complications. Complications leading to vision loss in the setting of uveitis include, but are not limited to macular edema, band keratopathy, cataract, glaucoma, as well as other factors such as retinal detachment and optic nerve damage. Additionally, uveitis is often linked to systemic inflammatory conditions, with 25%-50% of patients with uveitis having an associated diagnosis.
Uveitis epidemiology research in the United States (US) has produced variable incidence and prevalence rates, reflecting differences in geographic location, population size, and the underlying etiology of uveitis. The yearly incidence rates vary across different populations with the lowest reported from Kaiser Permanente Hawaii (25/100,000 persons) and the highest from the Northern California study (52/100,000), while the Optum administrative claims database found the highest prevalence of non-infectious uveitis of 121/100,000 persons. Similarly, cumulative prevalence rates have ranged from 57-115/100,000 persons. , The percentages of patients with low vision and other ocular complications have also shown considerable variability across studies.
This study aimed to assess both the incidence and prevalence of uveitis from 2013-2023 by utilizing the TriNetX US Network, a database comprised of clinical data from over 60 healthcare organizations and more than 100 million patients. In addition, we compared the demographics with the TriNetX database to the data from the 2023 US Census to assess for generalizability of our findings. Finally, we report the percentages of immunosuppressive medications used, associated systemic disorders, and uveitis-associated ocular complications.
METHODS
Data Source. This study utilized the TriNetX US Collaborative Network database with natural language processor (NLP). TriNetX is a deidentified multicenter-research network that employs the NLP program, which is a mining software that extracts written information from physician notes and clinical reports to create relevant International Classification for Disease, 10th Edition (ICD-10) coded information. The patient information was deidentified following the Health Insurance Portability and Accountability Act Privacy Rule as defined in Section >>164.514(b)(C). The study was determined to be exempt by the Drexel University College of Medicine Institutional Review Board due to data anonymization and was compliant with the tenets of the Declaration of Helsinki.
Study Cohort Identification. Subjects with a uveitis diagnosis between 2013-2023 were identified using ICD-10 codes (Supplemental Table 1). For years prior to 2019, the ICD-9 diagnosis codes were converted by TriNetX to the corresponding ICD-10 code. The data were also analyzed by the anatomic location of the uveitis based on Standardization of Uveitis Nomenclature classification: anterior, intermediate, posterior, or panuveitis. Percentages for uveitis subtypes were calculated using the number of patients with uveitis as the denominator, with each patient counted only once regardless of the number of subtypes recorded. As patients with multiple subtypes are included in the overall uveitis count, the sum of the anatomical subtype percentages exceeds 100%. Data collection occurred in November 2024 and codes can be found in Supplemental Table 1.
Systemic Immunosuppressive Medication Trends. Systemic immunosuppressive medications prescribed to subjects at the time of or after the diagnosis of uveitis were collected using RxNorm and Healthcare Common Procedure Coding System numbers, which can be found in Supplemental Table 2.
Associated Systemic Inflammatory Diseases. Systemic inflammatory diseases occurring with a diagnosis of uveitis were queried via ICD-10 codes, which can be found in Supplemental Table 3.
Ocular Complications. Ocular complications occurring at the same time or after the diagnosis of uveitis were collected: macular edema (H35.35X, H35.81X), band keratopathy (H18.42X), glaucoma (H40.X), cataract (H25.X, H26.X), and low vision and blindness (H54.X).
Statistical Analysis. For percentages, 95% confidence intervals (CI) were computed using the Wilson method. For means, 95% CIs were derived using standard errors based on a normal distribution. Chi-squared tests were used to assess differences in categorical variables across uveitis subtypes with anterior uveitis as the reference group. Z-tests for proportions were conducted to compare the relative frequency of specific conditions within uveitis subtypes. A p -value less than or equal to 0.05 was considered statistically significant. Negative binomial regression was performed using R (version 4.4.2, R core team, Vienna, Austria) with the MASS package to evaluate whether the incidence of overall uveitis and low vision in uveitis increased between the 2013-2018 and 2019-2023 periods, while accounting for overdispersion in the dataset.
Incidence and Prevalence. The incidence and prevalence of both uveitis and low vision within the cohort across anatomic subtypes from 2013-2023 were collected and analyzed using proprietary TriNetX software. The incidence and prevalence (yearly and cumulative) were calculated as cases per 100,000 persons.
Comparison of TriNetX to US Population. To assess the generalizability of findings, a comparison of age, gender, race, and ethnicity was made between the TriNetX population and data from the 2023 US Census, which can be found in Supplemental Table 4. Statistical equivalence for demographic proportions between the TriNetX US Collaborative Network population and the US 2023 Census population was assessed using the Two One-Sided Tests (TOST) of equivalence with ±2.5, ±5, and ±7.5 percentage point margins. The analysis was conducted with an alpha of 0.05 and 90% confidence intervals using R software.
RESULTS
Uveitis Demographics: Of the 109,026,851 subjects in the TriNetX database, 278,333 (0.26%) had a diagnosis of uveitis ( Table 1 ). The mean age was 56 years (Standard Deviation (SD) = 21). The majority were female (n = 149,186; 53.6%, 95% CI 53.4%-53.8%) and white (n = 150,578; 54.1%, 95% CI 53.9%-54.3%). Anterior uveitis (n = 209,073; 75.1%) was the most common anatomic subtype, followed by panuveitis (n = 52,196; 18.8%) ( P < .05).
| Demographics of Subjects with Uveitis by Anatomic Location | |||||
|---|---|---|---|---|---|
| Anatomic Location | Overall Uveitis | Anterior | Intermediate | Posterior | Panuveitis |
| Total Patients N; % | 278,333 a | 209,073; 75.1 | 8,867; 3.2 | 41,739; 15.0 | 52,196; 18.8 |
| Age | |||||
| Mean; SD (95% CI) | 56; 21 (55.9-56.1) | 56; 21 (55.9-56.0) | 49; 21 (48.6-49.4) | 58; 21 (57.8-58.2) | 58; 23 (57.8-58.2) |
| Gender N; % (95% CI) | |||||
| Female | 149,186; 53.6 (53.4-53.8) | 112,460; 53.8 (53.6-54.0) | 5,315; 59.9 (58.9-61.0) | 22,806; 54.6 (54.2-55.1) | 27,768; 53.2 (52.8-53.6) |
| Male | 123,886; 44.5 (44.3-44.7) | 92,640; 44.3 (44.1-44.5) | 3,407; 38.4 (37.4-39.4) | 18,340; 43.9 (43.5-44.4) | 23,431; 44.9 (44.5-45.3) |
| Unknown | 5,260; 1.9 (1.8-1.9) | 3,972; 1.9 (1.8-2.0) | 145; 1.6 (1.4-1.9) | 593; 1.4 (1.3-1.5) | 997; 1.9 (1.8-2.0) |
| Ethnicity N; % (95% CI) | |||||
| Non-Hispanic or Latino | 179,775; 64.6 (64.4-64.8) | 135,500; 64.8 (64.6-65.0) | 6,462; 72.9 (72.0-73.8) | 27,402; 65.7 (65.2-66.1) | 33,891; 64.9 (64.5-65.3) |
| Hispanic or Latino | 25,133; 9.0 (8.9-9.1) | 18,210; 8.7 (8.6-8.8) | 822; 9.3 (8.7-9.9) | 4,370; 10.5 (10.2-10.8) | 5,783; 11.1 (10.8-11.4) |
| Unknown | 73,424; 26.4 (26.2-26.5) | 55,363; 26.5 (26.3-26.7) | 1,583; 17.9 (17.1-18.7) | 9,967; 23.9 (23.5-24.3) | 12,522; 24.0 (23.6-24.4) |
| Race N; % (95% CI) | |||||
| White | 150,578; 54.1 (53.9-54.3) | 107,380; 51.4 (51.2-51.6) | 5,689; 64.2 (63.2-65.2) | 24,789; 59.4 (58.9-59.9) | 31,803; 60.9 (60.5-61.3) |
| Black | 62,152; 22.3 (22.2-22.5) | 52,833; 25.3 (25.1-25.5) | 1,295; 14.6 (13.9-15.34) | 6,257; 15.0 (14.7-15.3) | 8,435; 16.2 (15.8-16.5) |
| Asian | 8,016; 2.9 (2.8-2.9) | 5,854; 2.8 (2.7-2.9) | 234; 2.6 (2.3-3.0) | 1,398; 3.3 (3.2-3.5) | 1,519; 2.9 (2.8-3.1) |
| Native American | 1,419; 0.5 (0.5-0.5) | 1,066; 0.5 (0.4-0.5) | 48; 0.5 (0.4-0.7) | 213; 0.5 (0.4-0.6) | 298; 0.6 (0.5-0.6) |
| Native Hawaiian | 1,837; 0.7 (0.6-0.7) | 1,359; 0.7 (0.6-0.7) | 40; 0.5 (0.3-0.6) | 234; 0.6 (0.5-0.6) | 402; 0.7 (0.7-0.8) |
| Other | 12,219; 4.4 (4.3-4.5) | 8,718; 4.2 (4.1-4.3) | 482; 5.4 (5.0-5.9) | 2,141; 5.1 (4.9-5.3) | 2,813; 5.4 (5.2-5.6) |
| Unknown | 42,112;15.1 (15.0-15.3) | 31,863; 15.2 (15.1-15.4) | 1,079; 12.2 (11.5-12.9) | 6,707; 16.1 (15.7-16.4) | 6,926; 13.3 (13.0-13.6) |
Medications: Oral prednisone was the most frequently prescribed systemic immunosuppressive medication (n = 62,834; 22.6%, 95% CI 22.5%-22.8%), with usage varying by anatomic subtype. Glucocorticoids were also the most used class of medication (n = 62,964; 22.6%, 95% CI 22.5%-22.8%). Prednisone was most commonly prescribed in cases of posterior uveitis (n = 12,200; 29.2%, 95% CI 28.8%-29.6%) ( P < .05). Methotrexate was the most prevalent corticosteroid-sparing immunosuppressive, prescribed to 5.7% (95% CI 5.6%-5.8%) of uveitis patients (n = 15,817) ( P < .05). Other common biologics used included adalimumab (n = 11,566; 4.2%, 95% CI 4.1%-4.2%) and infliximab (n = 3,966; 1.4%, 95% CI 1.4%-1.5%) ( Table 2 ).
| Specific Immunosuppressant Use in Uveitis Overall and by Anatomic Subtype | |||||
|---|---|---|---|---|---|
| Overall Uveitis | Anterior | Intermediate | Posterior | Panuveitis | |
| Prednisone | 62,834; 22.6 (22.5-22.8) | 49,293; 23.6 (23.4-23.8) | 3,090; 34.9 (33.9-35.9) | 12,200; 29.2 (28.8-29.6) | 13,084; 25.1 (24.7-25.5) |
| Oral Prednisolone | 130; 0.05 (0.04-0.06) | 69; 0.03 (0.03-0.04) | ≤10 a ; 0.1 (0.02-0.13) | 25; 0.06 (0.04-0.09) | 44; 0.08 (0.06-0.1) |
| Methotrexate | 15,817; 5.7 (5.6-5.8) | 13,777; 6.6 (6.5-6.7) | 1,537;17.3 (16.6-18.2) | 2,953; 7.1 (6.8-7.3) | 3147; 6.0 (5.8-6.2) |
| Azathioprine | 3,614; 1.3 (1.3-1.3) | 2,904; 1.4 (1.3-1.4) | 183; 2.1 (1.8-2.4) | 894; 2.1 (2.0-2.3) | 622;1.2 (1.1-1.3) |
| Mycophenolate | 7,418; 2.7 (2.6-2.7) | 5,183; 2.5 (2.4-2.5) | 690; 7.8 (7.3-8.4) | 2,693; 6.5 (6.2-6.7) | 1,833; 3.5 (3.4-3.7) |
| Tacrolimus | 5,207; 1.9 (1.8-1.9) | 3,496; 1.7 (1.6-1.7) | 148; 1.7 (1.4-2.0) | 1192; 2.9 (2.7-3.0) | 1,091; 2.1 (2.0-2.2) |
| Oral Cyclosporine | 109; 0.04 (0.03-0.05) | 65; 0.03 (0.02-0.04) | 0; 0 (0-0.04) | 30; 0.07 (0.05-0.1) | 29; 0.06 (0.04-0.08) |
| Cyclophosphamide | 1,405; 0.5 (0.5-0.5) | 924; 0.4 (0.4-0.5) | 27; 0.3 (0.2-0.4) | 379; 0.9 (0.8-1.0) | 265; 0.5 (0.5-0.6) |
| Chlorambucil | 66; 0.02 (0.02-0.03) | 50; 0.02 (0.02-0.03) | ≤10 a ; 0.1 (0.02-0.1) | 16; 0.04 (0.02-0.06) | 11l 0.02 (0.01-0.04) |
| Adalimumab | 11,566; 4.2 (4.1-4.2) | 10,486; 5.0 (4.9-5.1) | 1,180;13.3 (12.6-14.1) | 1,994; 4.8 (4.6-5.0) | 2,266; 4.3 (4.2-4.5) |
| Infliximab | 3,966; 1.4 (1.4-1.5) | 3,650; 1.8 (1.7-1.8) | 340; 3.8 (3.5-4.3) | 606;1.5 (1.3-1.6) | 818; 1.6 (1.5-1.7) |
| Tocilizumab | 920; 0.3 (0.3-0.4) | 778; 0.4 (0.3-0.4) | 68; 0.8 (0.6-1.0) | 146; 0.4 (0.3-0.4) | 193; 0.4 (0.3-0.4) |
| Anakinra | 148; 0.05 (0.05-0.06) | 106; 0.05 (0.04-0.06) | ≤10 a ; 0.1 (0.02-0.1) | 31; 0.07 (0.05-0.1) | 26; 0.05 (0.03-0.07) |
| Golimumab | 682; 0.3 (0.2-0.3) | 621; 0.3 (0.3-0.3) | 21; 0.2 (0.2-0.4) | 57; 0.1 (0.1-0.2) | 62; 0.1 (0.09-0.2) |
| Certolizumab Pegol | 762; 0.3 (0.3-0.3) | 696; 0.3 (0.3-0.4) | 31; 0.4 (0.3-0.5) | 52l 0.1 (0.09-0.16) | 63; 0.1 (0.09-0.2) |
| Etanercept | 1,767; 0.6 (0.6-0.7) | 1582; 0.8 (0.7-0.8) | 33; 0.4 (0.3-0.5) | 133; 0.3 (0.3-0.4) | 158; 0.3 (0.3-0.4) |
| Rituximab | 2,117; 0.8 (0.7-0.8) | 1436; 0.7 (0.7-0.7) | 136; 1.5 (1.3-1.8) | 632; 1.5 (1.4-1.6) | 379; 0.7 (0.7-0.8) |
| Classes of Immunosuppressant Use in Uveitis Overall and by Anatomic Subtype | |||||
| Glucocorticoids | 62,964; 22.6 (22.5-22.8) | 49,362; 23.6 (23.4-23.8) | 3,100; 35.0 (34.0-36.0) | 12,225; 29.3 (28.9-29.7) | 13,128; 25.1 (24.7-25.5) |
| Antimetabolites | 26,849; 9.7 (9.5-9.8) | 21,864; 10.5 (10.3-10.6) | 2,410; 27.2 (26.3-28.2) | 6,540; 15.7 (5.3-16.0) | 5602; 10.7 (10.5-11.0) |
| Calcineurin Inhibitors | 5,316; 1.9 (1.9-2.0) | 3,561; 1.7 (1.7-1.8) | 148; 1.7 (1.4-2.0) | 1222; 2.9 (2.8-3.1) | 1,120; 2.2 (2.0-2.3) |
| Alkylating Agents | 1,471; 0.5 (0.5-0.6) | 974; 0.5 (0.4-0.5) | 37; 0.4 (0.3-0.6) | 395; 1.0 (0.9-1.0) | 276; 0.5 (0.47-0.59) |
| Biologics | 21,928; 7.9 (7.8-8.0) | 19,350; 9.3 (9.1-9.4) | 1,819; 20.5 (19.7-21.4) | 3,651; 8.8 (8.5-9.0) | 3,965; 7.7 (7.4-7.8) |
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