Abstract
Purpose:
To determine classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis
Design:
Machine learning of cases with spondyloarthritis/HLA-B27-associated anterior uveitis and 8 other anterior uveitides.
Methods:
Cases of anterior uveitides were collected in an informatics-designed preliminary database, and a final database was constructed of cases achieving supermajority agreement on the diagnosis, using formal consensus techniques. Cases were split into a training set and a validation set. Machine learning using multinomial logistic regression was used on the training set to determine a parsimonious set of criteria that minimized the misclassification rate among the anterior uveitides. The resulting criteria were evaluated on the validation set.
Results:
One thousand eighty-three cases of anterior uveitides, including 184 cases of spondyloarthritis/HLA-B27-associated anterior uveitis, were evaluated by machine learning. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI 92.4, 98.6). Key criteria for spondyloarthritis/HLA-B27-associated anterior uveitis included 1) acute or recurrent acute unilateral or unilateral alternating anterior uveitis with either spondyloarthritis or a positive test for HLA-B27 or 2) chronic anterior uveitis with a history of the classic course and either spondyloarthritis or HLA-B27 or 3) anterior uveitis with both spondyloarthritis and HLA-B27. The misclassification rates for spondyloarthritis/HLA-B27-associated anterior uveitis were 0% in the training set and 3.6% in the validation set, respectively.
Conclusions:
The criteria for spondyloarthritis/HLA-B27-associated anterior uveitis had a low misclassification rate and appeared to perform well enough for use in clinical and translational research.
PRECIS
Using a formalized approach to developing classification criteria, including informatics-based case collection, consensus-technique-based case selection, and machine learning, classification criteria for spondyloarthritis/HLA-B27-associated anterior uveitis were developed. Key criteria included anterior uveitis with 2 of 3 features: 1) characteristic course of acute or recurrent acute, unilateral or unilateral alternating, anterior uveitis; 2) spondyloarthritis; and 3) HLA-B27. The resulting criteria had a low misclassification rate.
Spondyloarthritis (SpA) refers to a spectrum of inflammatory arthritides with overlapping features that includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and arthritis related to inflammatory bowel disease.1,2 The prevalence of spondyloarthritis is estimated at ~1.5 to 2.0%, and that of ankylosing spondylitis at ~0.5 to 1.0%.2 The diseases are linked to the HLA allele HLA-B27 with population disease frequency variation due, at least in part, to the population gene frequency variation of HLA-B27. Ninety to 95% of Caucasian patients with ankylosing spondylitis will possess HLA-B27 and 70 to 80% of patients with reactive arthritis, compared to a general Caucasian population gene frequency for HLA-B27 of ~8%. The frequency of HLA-B27 among patients with psoriatic arthritis and inflammatory bowel disease-associated arthritis (enteropathic arthritis) is lower, ~24% and 7% respectively, but substantially higher among patients with psoriatic spondylitis and spondylitis/sacroiliitis with inflammatory bowel disease, ~60 to 70%.1
Predominant axial involvement (axial SpA) is the hallmark of ankylosing spondylitis and is characterized by inflammatory back pain with marked morning stiffness and worsening of symptoms with inactivity. Sacroiliac joint involvement is classic, and there may be variable peripheral joint involvement as well. Peripheral SpA typically involves non-axial joints with limited axial involvement and includes reactive arthritis, psoriatic arthritis, and inflammatory bowel disease-related arthritis.1,2
Classification criteria were first developed for ankylosing spondylitis in 1961 with the Rome criteria, with subsequent development of the New York criteria and the modified New York criteria in 1984. The New York and modified New York criteria require the radiographic demonstration of sacroiliitis. Early radiographic changes are difficult to detect and may take up to 10 years after disease onset to become evident. Computerized tomographic (CT) imaging and magnetic resonance imaging (MRI) are more sensitive than conventional X-rays, with CT superior for bony involvement and MRI preferred for soft tissue inflammation.2–4 Classification criteria for psoriatic arthritis were first proposed by Moll and Wright in 1973, and evolved over time into the CASPAR criteria, published in 2006.2,5
More recently SpA has been divided into axial SpA and peripheral SpA, based on the presence or absence of axial (spinal and sacroiliac) arthritis. The Assessment of SpondyloArthritis international Society (ASAS) published criteria for axial SpA in 2009, which divided axial SpA into radiographic and non-radiographic axial SpA, and for peripheral SpA in 2011.2,6–8 The ASAS criteria for axial SpA are outlined in Table 1 and for peripheral SpA in Table 2. The ASAS criteria are more inclusive than previous sets as radiologic changes are not required.
Table 1.
ASAS Classification Criteria for Axial Spondyloarthritis (SpA)
| In patients with back pain ≥3 months and age onset <45 years | ||
| Sacroiliitis on imaging plus ≥1 SpA feature * | OR | HLA-B27 plus ≥2 SpA features * |
| SpA features: | Sacroiliitis on imaging: | |
| • Inflammatory back pain | • Active inflammation on MRI† highly suggestive of sacroiliitis with SpA | |
| • Arthritis | ||
| • Enthesitis (heel) | or | |
| • Uveitis | • Definite radiographic sacroiliitis according to the modified New York criteria | |
| • Dactylitis | ||
| • Psoriasis | ||
| • Crohn disease/ulcerative colitis | ||
| • Good response to NSAIDs‡ | ||
| • Family history for SpA | ||
| • HLA-B27 | ||
| • Elevated CRP§ | ||
SpA = spondyloarthritis.
MRI = magnetic resonance imaging.
NSAIDs = non-steroidal anti-inflammatory drugs.
CRP = C-reactive protein.
Adapted from Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–83.
Table 2.
ASAS Classification Criteria for Peripheral Spondyloarthritis (SpA)
| Arthritis (peripheral) or enthesitis or dactylitis |
| plus |
| ≥1 Spondyloarthritis feature |
| • Uveitis |
| • Psoriasis |
| • Crohn disease/ulcerative colitis |
| • Preceding infection |
| • HLA-B27 |
| • Sacroiliitis on imaging |
| OR |
| ≥2 other Spondyloarthritis features |
| • Arthritis |
| • Enthesitis |
| • Dactylitis |
| • Inflammatory back pain |
| • Family history for SpA |
Adapted from Rudwaleit M, van der Heijde D, Landewe R, et al. The Assessment of SpondyloArthritis internation Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25–31.
Among the most common extra-articular features of SpA is uveitis.1,2 Estimates of the cumulative risk of uveitis among patients with ankylosing spondylitis run as high as 55%, but typically are reported as ~25%. The risk appears similar among patients with reactive arthritis, but lower, in the 10 to 20% range, for enteropathic arthritis and psoriatic arthritis.1 The typical pattern for SpA-associated uveitis is a recurrent acute, unilateral or unilateral alternating, anterior uveitis.1,9 This type of uveitis shares with SpA HLA-B27 as a risk factor. Approximately 60% of patients with recurrent acute unilateral anterior uveitis will be HLA-B27-positive and 80% of those with recurrent acute unilateral alternating anterior uveitis will be HLA-B27-positive.9 Among patients with uveitis and HLA-B27 the prevalence of SpA is estimated at 58 to 78%.10–12 In one 11-year nationwide incidence study, the incidence of ankylosing spondylitis among patients with acute anterior uveitis was 121.5/100,000 person years, which was ~17-fold greater than among patients without acute anterior uveitis.13
The Standardization of Uveitis Nomenclature (SUN) Working Group is an international collaboration, which has developed classification criteria for 25 of the most common uveitides using a formal approach to development of classification criteria.14–20 Among the uveitides studied was SpA/HLA-B27-associated anterior uveitis.15,17,20
Methods
The SUN Developing Classification Criteria for the Uveitides project proceeded in four phases as previously described: 1) informatics, 2) case collection, 3) case selection, and 4) machine learning.16–18,20
Informatics.
As previously described, the consensus-based informatics phase permitted the development of a standardized vocabulary and the development of a standardized, menu-driven hierarchical case collection instrument.16
Case collection and case selection.
Information was entered into the SUN preliminary database by the 76 contributing investigators for each disease as previously described.18,20 Cases in the preliminary database were reviewed by committees of 9 investigators for selection into the final database, using formal consensus techniques described in the accompanying article.18,20 Because the goal was to develop classification criteria, only cases with a supermajority agreement (>75%) that the case was the disease were retained in the final database (i.e. were “selected”).
Machine learning.
The final database then was randomly separated into a training set (~85% of cases) and a validation set (~15% of cases) for each disease as described in the accompanying article.20 Machine learning was used on the training set to determine criteria that minimized misclassification. The criteria then were tested on the validation set; for both the training set and the validation set, the misclassification rate was calculated for each disease. The misclassification rate was the proportion of cases classified incorrectly by the machine learning algorithm when compared to the consensus diagnosis. For SpA/HLA-B27-associated anterior uveitis, the diseases against which it was evaluated were: cytomegalovirus (CMV) anterior uveitis, Herpes simplex virus (HSV) anterior uveitis, Varicella zoster virus (VZV) anterior uveitis, juvenile idiopathic arthritis (JIA)-associated anterior uveitis, tubulointerstitial nephritis with uveitis (TINU), Fuchs uveitis syndrome, sarcoidosis-associated anterior uveitis, and syphilitic anterior uveitis.
Comparison of cases with acute anterior uveitis and chronic anterior uveitis.
Comparison of cases with acute anterior uveitis vs. those with chronic anterior uveitis for categorical variables was performed with the chi-square test or the Fisher’s exact test if a cell was less than 5. For categorical variables with multiple grades, grades above and below the median were compared. For continuous variables, the Wilcoxon rank sum test was used. P-values are nominal and two-sided.
The study adhered to the principles of the Declaration of Helsinki. Institutional Review Boards (IRBs) at each participating center reviewed and approved the study; the study typically was considered either minimal risk or exempt by the individual IRBs.
Results
Two hundred fifty-one cases of Sp/HLA-B27-associated anterior uveitis were collected, and 184 (74%) achieved supermajority agreement on the diagnosis during the “selection” phase and were used in the machine learning phase. These cases of SpA/HLA-B27-associated anterior uveitis were compared to cases of other anterior uveitides, including 89 cases of CMV anterior uveitis, 123 cases of VZV anterior uveitis, 146 cases of Fuchs Uveitis Syndrome, 202 cases of JIA-associated anterior uveitis, 101 cases of HSV anterior uveitis, 94 cases of TINU, 112 cases of sarcoidosis-associated anterior uveitis, and 32 cases of syphilitic anterior uveitis. The characteristics at presentation to a SUN Working Group Investigator of cases with spondyloarthritis/HLA-B27 anterior uveitis are listed in Table 3. A comparison of cases with acute or recurrent acute anterior uveitis to those with chronic anterior uveitis is listed in Table 4. The criteria developed after machine learning are listed in Table 5. Key features of the criteria include anterior uveitis with either an acute or recurrent acute course or if a chronic course, a history of a recurrent acute course evolving into a chronic course, and the presence of either HLA-B27 or a SpA or anterior uveitis in the presence of both HLA-B27 and SpA. The overall accuracy for anterior uveitides was 97.5% in the training set and 96.7% in the validation set (95% CI 92.4, 98.6).20 The misclassification rate for SpA/HLA-B27-associated anterior uveitis in the training set was 0% and in the validation set 3.6%.
Table 3.
Characteristics of Cases with Spondyloarthritis/HLA-B27-associated Anterior Uveitis
| Characteristic | Result |
|---|---|
| Number cases | 184 |
| Demographics | |
| Age, median, years (25th 75th percentile) | 37 (30, 46) |
| Age category, years (%) | |
| ≤16 | 4 |
| 17–50 | 76 |
| 51–59 | 11 |
| ≥60 | 10 |
| Gender (%) | |
| Men | 54 |
| Women | 46 |
| Race/ethnicity (%) | |
| White, non-Hispanic | 73 |
| Black, non-Hispanic | 4 |
| Hispanic | 2 |
| Asian, Pacific Islander | 13 |
| Other | 3 |
| Missing/unknown | 5 |
| Uveitis History | |
| Uveitis course (%) | |
| Acute, monophasic | 15 |
| Acute, recurrent | 61 |
| Chronic | 17 |
| Indeterminate | 8 |
| Laterality (%) | |
| Unilateral | 60 |
| Unilateral, alternating | 36 |
| Bilateral | 4 |
| Ophthalmic examination | |
| Cornea | |
| No keratitis | 100 |
| Keratitis | 0 |
| Keratic precipitates (%) | |
| None | 0 |
| Fine | 41 |
| Round | 54 |
| Stellate | 5 |
| Mutton Fat | 0 |
| Other | 0 |
| Anterior chamber cells (%) | |
| Grade ½+ | 8 |
| 1+ | 23 |
| 2+ | 35 |
| 3+ | 24 |
| 4+ | 10 |
| Hypopyon (%) | 10 |
| Anterior chamber flare (%) | |
| Grade 0 | 28 |
| 1+ | 36 |
| 2+ | 18 |
| 3+ | 7 |
| 4+ | 11 |
| Iris (%) | |
| Normal | 61 |
| Posterior synechiae | 38 |
| Sectoral iris atrophy | 1 |
| Patchy iris atrophy | 1 |
| Diffuse iris atrophy | 0 |
| Heterochromia | 0 |
| Intraocular pressure (IOP), involved eyes | |
| Median, mm Hg (25th, 75th percentile) | 13 (12, 16) |
| Proportion patients with IOP>24 mm Hg either eye (%) | 2 |
| Vitreous cells (%) | |
| Grade 0 | 68 |
| ½+ | 17 |
| 1+ | 12 |
| 2+ | 2 |
| 3+ | 1 |
| 4+ | 0 |
| Systemic disease (%) | |
| Spondyloarthritis | 53 |
| Psoriasis | 6 |
| Inflammatory bowel disease | 2 |
| Laboratory | |
| Positive HLA-B27* (%) | 97 |
179 positive of 184 patients tested.
Table 4.
Comparison of Characteristics of Cases with Spondyloarthritis/HLA-B27-associated Acute vs Chronic Anterior Uveitis
| Characteristic | Acute anterior uveitis* | Chronic anterior uveitis† | P-value |
|---|---|---|---|
| Number cases | 155 | 29 | |
| Demographics | |||
| Age, median, years (25th 75th percentile) | 37 (29, 46) | 37 (35, 40) | 0.78 |
| Gender (%) | 0.17 | ||
| Men | 52 | 65 | |
| Women | 48 | 35 | |
| Race/ethnicity (%) | 0.09 | ||
| White, non-Hispanic | 73 | 86 | |
| Black, non-Hispanic | 4 | 4 | |
| Hispanic | 0 | 0 | |
| Asian, Pacific Islander | 16 | 0 | |
| Other | 3 | 4 | |
| Missing/unknown | 4 | 6 | |
| Uveitis History | |||
| Laterality (%) | <0.001 | ||
| Unilateral | 56 | 79 | |
| Unilateral, alternating | 43 | 0 | |
| Bilateral | 1 | 21 | |
| Ophthalmic examination | |||
| Keratic precipitates (%) | 0.79 | ||
| None | 40 | 45 | |
| Fine | 55 | 48 | |
| Other | 5 | 7 | |
| Anterior chamber cells (%) | 0.52 | ||
| ≤2+ | 64 | 79 | |
| >2+ | 36 | 21 | |
| Hypopyon (%) | 10 | 14 | 0.51 |
| Iris (%) | 0.19 | ||
| Normal | 65 | 52 | |
| Posterior synechiae | 35 | 48 | |
| Intraocular pressure (IOP), involved eyes | 14 (13, 17) | 15 (13, 18) | 0.31 |
| Median, mm Hg (25th, 75th percentile) | |||
| Vitreous cells (%) | 0.52 | ||
| Grade 0 | 68 | 66 | |
| >½+ | 32 | 34 | |
| Systemic disease (%) | |||
| Spondyloarthritis (axial or peripheral) | 48 | 72 | 0.03 |
| Inflammatory bowel disease | 3 | 7 | |
| Laboratory | |||
| Positive HLA-B27 (%) | 98 | 97 | 0.61 |
Includes 113 cases with recurrent acute anterior uveitis and 42 cases with single episode of acute anterior uveitis.
Includes 8 cases with history or acute anterior uveitis and crescendo pattern into chronic anterior uveitis.
Table 5.
Classification Criteria for Spondyloarthritis/HLA-B27-associated Anterior Uveitis
| Criteria |
| 1. Evidence of anterior uveitis |
| a. anterior chamber cells |
| b. if anterior vitreous cells are present, severity is less than anterior chamber inflammation |
| AND either (both #2 and #3) OR #4 |
| 2. Characteristic uveitis course |
| a. Acute or recurrent acute, unilateral or unilateral alternating course OR |
| b. Chronic course with a history of a recurrent acute, unilateral or unilateral alternating course evolving into chronic course |
| AND |
| 3. ASAS-defined spondyloarthritis (axial or peripheral) and/or HLA-B27-positive |
| OR |
| 4. Chronic uveitis with both ASAS-defined spondyloarthritis (axial or peripheral) AND HLA-B27-positive |
| Exclusions |
| 1. Positive serology for syphilis using a treponemal test |
| 2. Evidence of sarcoidosis (either bilateral hilar adenopathy oi chest imaging or tissue biopsy demonstrating non-caseating granulomata) |
| 3. Aqueous specimen PCR† positive for cytomegalovirus, Herpes simplex virus or Varicella zoster virus |
Discussion
Numerous case series have documented the overlapping relationships among SpA, HLA-B27, and acute anterior uveitis.1,9–13 Nevertheless, HLA-B27 is a risk factor, and these diseases are not simple Mendelian genetic disorders. Even among Caucasians with ankylosing spondylitis, the most closely linked SpA to HLA-B27, 5 to 10% will be HLA-B27 negative.1 With a population frequency for HLA-B27 of ~8% and an ankylosing spondylitis prevalence of ~1%, it is the minority of patients with HLA-B27 that will develop SpA. Furthermore, among patients with other defined uveitides, 8% would be expected to be HLA-B27 positive by chance alone. Hence, the presence of HLA-B27 alone is not diagnostic of an SpA/HLA-B27-associated anterior uveitis, and the criteria can be distilled as requiring anterior uveitis and 2 of the 3 features: classic presentation, HLA-B27, or SpA.
Although the large majority of cases had the classic course, namely acute or recurrent acute, unilateral or unilateral alternating, anterior uveitis, ~15% in the SUN data base had a chronic uveitis upon presentation to a SUN investigator, a result seen in other large cohorts of patients with SpA.21 Several of the cases in the SUN database had a history of a classic pattern that evolved over time into a chronic uveitis, a phenomenon which previously has been described11. The comparison of cases with acute vs chronic uveitis suggested that chronic uveitis cases were more likely to have a diagnosed SpA. The greater frequency of SpA among patients with chronic uveitis and SpA/HLA-B27-associated anterior uveitis may reflect the uncertainty of the relationship of HLA-B27 alone with chronic anterior uveitis (associated disease vs chance) in the absence of SpA. There was a sentiment among the case selection committee that patients with psoriatic arthritis are more likely to have atypical SpA/HLA-B27-associated uveitis, namely chronic or bilateral disease, which appeared to be correct when the data were reviewed, but the data set lacked sufficient power for formal analysis of this impression.
The case collection phase utilized retrospective data, the diagnosis of SpA was a clinical one, and likely did not necessarily use the ASAS criteria. The ASAS criteria were developed to enable earlier diagnosis of SpA, as they do not require radiographic confirmation of sacroiliitis for axial SpA, which can take years to develop. Although we could not verify that all cases included in the SpA/HLA-B27 anterior uveitis database and identified as having an SpA would have fulfilled the ASAS criteria, criteria for its diagnosis are needed going forward, and the ASAS criteria6–8 were chosen by the SUN Working Group.
Although classically associated with endophthalmitis and Behçet disease, hypopyon can be seen with severe attacks of SpA/ HLA-B27-associated anterior uveitis. 22,23 One study estimated the 10-year incidence of hypopyon uveitis among patients with HLA-B27-associated uveitis to be 17%.23 Risk factors for hypopyon uveitis included Behçet disease (adjusted relative risk [RR] 5.30), SpA (RR 2.86) and HLA-B27 (RR 2.04).23 In the United States hypopyon uveitis is seen most often among patients with SpA/HLA-B27 anterior uveitis, whereas in regions where Behçet disease is more prevalent than in the United States, it will be seen more often with Behçet disease.22,23 Nevertheless, because of its presence in several uveitides, hypopyon does not appear to be a discriminatory factor in classifying the uveitides.
The presence of any of the exclusions in Table 5 suggests an alternate diagnosis, and the diagnosis of spondyloarthritis/HLA-B27-associated anterior uveitis should not be made in their presence. In prospective studies many of these tests will be performed routinely, and the alternative diagnoses excluded. However, in retrospective studies based on clinical care, not all of these tests may have been performed. Hence the presence of an exclusionary criterion excludes spondyloarthritis/HLA-B27-associated anterior uveitis, but the absence of such testing does not exclude the diagnosis of spondyloarthritis/HLA-B27-associated anterior uveitis if the criteria for the diagnosis are met.
Classification criteria are employed to diagnose individual diseases for research purposes.19 Classification criteria differ from clinical diagnostic criteria, in that although both seek to minimize misclassification, when a trade-off is needed, diagnostic criteria typically emphasize sensitivity, whereas classification criteria emphasize specificity,19 in order to define a homogeneous group of patients for inclusion in research studies and limit the inclusion of patients without the disease in question that might confound the data. The machine learning process employed did not explicitly use sensitivity and specificity; instead it minimized the misclassification rate. Because we were developing classification criteria and because the typical agreement between two uveitis experts on diagnosis is moderate at best,18 the selection of cases for the final database (“case selection”) included only cases which achieved supermajority agreement on the diagnosis. As such, some cases that clinicians would diagnose with SpA/HLA-B27-associated uveitis might not be so classified by classification criteria. The selection of cases during the case selection phase of cases that achieved supermajority agreement on the diagnosis for inclusion in the final database was used in part because we were developing classification criteria.
In conclusion, the criteria for SpA/HLA-B27-associated anterior uveitis outlined in Table 5 appear to perform sufficiently well for use as classification criteria in clinical research.
Grant support:
Supported by grant R01 EY026593 from the National Eye Institute, the National Institutes of Health, Bethesda, MD, USA; the David Brown Fund, New York, NY, USA; the Jillian M. And Lawrence A. Neubauer Foundation, New York, NY, USA; and the New York Eye and Ear Foundation, New York, NY, USA.
Footnotes
Writing committee: Douglas A. Jabs, MD, MBA2,3, Nisha R. Acharya, MD4, Soon-Phaik Chee, FRCOphth, FRCS (G), FRCS (Ed), MMed (Singapore)5, Debra Goldstein, MD6, Peter McCluskey, MD7, Philip I. Murray, PhD, FRCP, FRCS, FRCOphth8, Neal Oden, PhD9, Alan G. Palestine, MD10, James T. Rosenbaum, MD11,12, Jennifer E. Thorne, MD, PhD2,3, Brett E. Trusko, PhD, MBA.13
Affiliations: 1Members of the SUN Working Group are listed online at ajo.com. From 2the Department of Epidemiology, the Johns Hopkins University Bloomberg School of Public Health, and 3the Wilmer Eye Institute, the Department of Ophthalmology, the Johns Hopkins University School of Medicine, Baltimore, MD, USA; 4the Francis I. Proctor Foundation, the University of California, San Francisco School of Medicine, San Francisco, CA, USA; 5Singapore National Eye Centre, Singapore Eye Research Institute, Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Duke-NUS Medical School, Singapore; 6the Department of Ophthalmology, the Northwestern Feinberg School of Medicine, Chicago, IL, USA; 7the Save Sight Institute, Department of Ophthalmology, University of Sydney School of Medicine, Sydney, NSW, Australia; 8the Academic Unit of Ophthalmology, University of Birmingham, Birmingham, UK; 9the Emmes Company, LLC, Rockville, MD, USA; 10the Department of Ophthalmology, University of Colorado School of Medicine, Aurora, Co, USA; 11the Departments of Medicine and Ophthalmology, Oregon Health and Science University, Portland, OR, USA; 12the Legacy Devers Eye Institute, Portland, OR, USA; 13the Department of Medicine, Texas A&M University, College Station, TX, USA.
Conflict of Interest: Douglas A. Jabs: none; Nisha Acharya: none; Soon-Phaik Chee: none; Debra Goldstein: none; Peter McCluskey: none; Philip I. Murray: none; Neal Oden: none; Alan G. Palestine: none; James T. Rosenbaum: consultant: AbbVie, Eyevensys, Gilead, Horizon, Janssen, Novartis, Roche, Santen, UCB; grant support: Pfizer; Jennifer E. Thorne: Dr. Thorne engaged in part of this research as a consultant and was compensated for the consulting service; Brett E. Trusko: none.
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REFERENCES
- 1.Thorne JE, Jabs DA. The eye in rheumatic disease. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatology, 4th edition. Philadelphia, Elsevier, 2008;pp 261–8. [Google Scholar]
- 2.Rudwaleit M, Taylor WJ. Classification criteria for psoriatic arthritis and ankylosing spondylitis/axial spondyloarthritis. Best Practice & Research Clinical Rheumatology. 2010;24:589–604. [DOI] [PubMed] [Google Scholar]
- 3.van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361–8. [DOI] [PubMed] [Google Scholar]
- 4.Goie The HS, Steven MM, van der Linden SM, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis: a compariaon of the Rome, New York, and modified New York criteria in patients with a positive clinical history screening test for ankylosing spondylitis. Br J Rheumatol 1985;24:242–9. [DOI] [PubMed] [Google Scholar]
- 5.Taylor W, Gladman D, Helliwell P, Marchesoni A, Mease P, Mielants H and the CASPAR Study Group. Classification criteria for psoriatic arthritis. Arthritis Rheum 2006;54:2665–73. [DOI] [PubMed] [Google Scholar]
- 6.Rudwaleit M, Landewe R, van der Heijde D, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part I): classification of paper patients by expert opinion including uncertainty appraisal. Ann Rheum Dis 2009;68:770–6. [DOI] [PubMed] [Google Scholar]
- 7.Rudwaleit M, van der Heijde D, Landewe R, et al. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis 2009;68:777–83. [DOI] [PubMed] [Google Scholar]
- 8.Rudwaleit M, van der Heijde D, Landewe R, et al. The Assessment of SpondyloArthritis internation Society classification criteria for peripheral spondyloarthritis and for spondyloarthritis in general. Ann Rheum Dis 2011;70:25–31. [DOI] [PubMed] [Google Scholar]
- 9.Rosenbaum JT. Characterization of uveitis associated with spondyloarthritis. J Rheumatol 1989;16:792–6. [PubMed] [Google Scholar]
- 10.Linssen A, Meeknen C. outcomes of HLA-B27-positive and HLA-B27-negative acute anterior uveitis. Am J Ophthalmol 1995;120:351–61. [DOI] [PubMed] [Google Scholar]
- 11.Tay-Kearney ML, Schwam BL, Lowder C, Dunn JP, Meisler DM, Vitale S, Jabs DA. Clinical features and associated systemic diseases of HLA-B27 uveitis. Am J Ophthalmol 996;121:47–56. [DOI] [PubMed] [Google Scholar]
- 12.Monnet D, Breban M, Hudry C, Dougados M, Brezin AP. Ophthalmic findings and frequency of extraocular manifestations in patients with HLA-B27 uveitis: a study of 175 cases. Ophthalmology 2004;111:802–9. [DOI] [PubMed] [Google Scholar]
- 13.Oh BL, Lee EY, Lee HY, Yu HG. Recurrent acute anterior uveitis and subsequent incidence of ankylosing spondylitis: a nationwide cohort study from 2002 to 2013. Arthritis Res Ther 2018;7:22. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Jabs DA, Rosenbaum JT, Nussenblatt RB, the Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Report of the first international workshop. Am J Ophthalmol 2005;140:509–16. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Jabs DA, Busingye J. Approach to the diagnosis of the uveitides. Am J Ophthalmol 2013;156:228–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Trusko B, Thorne J, Jabs D, et al. Standardization of Uveitis Nomenclature Working Group. The SUN Project. Development of a clinical evidence base utilizing informatics tools and techniques. Methods Inf Med 2013;52:259–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Okada AA, Jabs DA. The SUN Project. The future is here. Arch Ophthalmol 2013;131:787–9. [DOI] [PubMed] [Google Scholar]
- 18.Jabs DA, Dick A, Doucette JT, Gupta A, Lightman S, McCluskey P, Okada AA, Palestine AG, Rosenbaum JT, Saleem SM, Thorne J, Trusko, B for the Standardization of Uveitis Nomenclature Working Group. Interobserver agreement among uveitis experts on uveitic diagnoses: the Standard of Uveitis Nomenclature experience. Am J Ophthalmol 2018; 186:19–24. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Aggarwal R, Ringold S, Khanna D, et al. Distinctions between diagnostic and classification criteria. Arthritis Care Res 2015;67(7):891–897. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.The Standardization of Uveitis Nomenclature (SUN) Working Group. Development of classification criteria for the uveitides. Am J Ophthalmol 2020;volume:pp. [DOI] [PubMed] [Google Scholar]
- 21.Zeboulon N, Dougados M, Gossec L. Prevalence and characteristics of uveitis in the spondyloarthropathies: a systematic literature review. Ann Rheum Dis 2008;67:955–9. [DOI] [PubMed] [Google Scholar]
- 22.D’Alessandro LP, Forster DJ, Rao NA. Anterior uveitis and hypopyon. Am J Ophthalmol 1991;112:317–21. [DOI] [PubMed] [Google Scholar]
- 23.Zaidi AA, Ying GS, Daniel E, et al. Hypopyon in patients with uveitis. Ophthalmology 2010;117:366–72. [DOI] [PMC free article] [PubMed] [Google Scholar]