The SUN II classification criteria are a classification system published in 2021 in the American Journal of Ophthalmology by the Standardization of Uveitis Nomenclature (SUN) Working Group. They present reproducible classification criteria for the 25 most common types of uveitis.
Uveitis is the fifth leading cause of blindness in developed countries. Traditionally, anatomical classification based on the site of inflammation (anterior, intermediate, posterior, and panuveitis) has been used. However, even within the same anatomical site, the etiology, clinical course, and prognosis differ. Before 2021, there was no validated approach to systematically classify individual uveitis entities. Consensus among experts was only moderate, and uniformity in ophthalmic literature was lacking.
The purpose of the SUN II classification criteria is to ensure homogeneity of patient populations in research. To maximize the probability that all study participants have the disease in question, the criteria are designed with an emphasis on specificity.
The SUN II classification criteria are for research purposes and prioritize specificity. It is possible for a clinically diagnosed patient not to meet the classification criteria1). The classification criteria aim to homogenize patient populations in research and do not negate clinical diagnosis.
The SUN II classification criteria target 25 types of uveitis. They are organized along two axes: anatomical classification (anterior, intermediate, posterior, and panuveitis) and etiological classification (infectious, systemic disease-associated, and ocular-limited).
The basic classification of uveitis is as follows:
Anterior uveitis includes 4 infectious diseases, 4 systemic disease-related diseases, and 1 ocular-limited disease.
Infectious
CMV anterior uveitis: Positive CMV-PCR in aqueous humor is required.
Herpes simplex virus (HSV) anterior uveitis: Unilateral, with positive PCR in aqueous humor or sectoral iris atrophy as criteria.
Varicella-zoster virus (VZV) anterior uveitis: Unilateral, with positive PCR in aqueous humor or cutaneous herpes zoster as criteria.
Syphilitic anterior uveitis: Positive treponemal test is required.
Systemic Disease-Related
Juvenile idiopathic arthritis-associated anterior uveitis: Chronic course and association with juvenile idiopathic arthritis (e.g., oligoarthritis) are criteria.
HLA-B27-associated anterior uveitis: Acute and recurrent, with spondyloarthritis or HLA-B27 positivity.
Tubulointerstitial nephritis and uveitis syndrome (TINU): Evidence of anterior uveitis and tubulointerstitial nephritis is required.
Sarcoidosis-related: Non-caseating granuloma or bilateral hilar lymphadenopathy is a criterion1).
Fuchs uveitis syndrome (ocular-limited) is unilateral. Iris heterochromia or diffuse iris atrophy and stellate keratic precipitates are characteristic findings.
Intermediate uveitis has its main site of inflammation in the vitreous. In 2005, the SUN Working Group defined pars planitis as only idiopathic conditions with peripheral white exudates (snowbank) and snowball vitreous opacities. In Europe and the United States, it accounts for about 15% of all uveitis cases, but in Japan, the frequency is low at 1–2%.
| Disease name | Etiology | Major criteria |
|---|---|---|
| Syphilitic intermediate uveitis | Infectious | Positive syphilis test |
| MS-associated intermediate uveitis | Systemic disease-related | MS by McDonald criteria |
| Sarcoidosis-associated | Systemic disease-related | Non-caseating granuloma, etc. |
Ocular-limited types include pars planitis (with snowballs/snowbanks) and non-pars planitis type (without). In both, multiple sclerosis, syphilis, sarcoidosis, and Lyme disease are exclusion criteria.
Posterior uveitis includes 5 infectious diseases, 1 systemic disease-related, and 6 ocular-limited diseases.
The main classification criteria for infectious posterior uveitis are as follows.
Ocular-limited forms include acute posterior multifocal placoid pigment epitheliopathy (APMPPE), birdshot retinochoroidopathy, multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis, punctate inner choroidopathy (PIC), and serpiginous choroiditis.
Panuveitis includes infectious (syphilis, tuberculosis), systemic disease-associated (Behçet’s disease, sarcoidosis), and ocular-limited (sympathetic ophthalmia, Vogt-Koyanagi-Harada disease) forms. For Vogt-Koyanagi-Harada disease, separate criteria are set for the early and late stages.
The SUN II classification covers 25 representative types of uveitis and does not encompass all forms of uveitis. Diseases not included in the classification should be diagnosed based on conventional clinical diagnostic criteria.
The SUN II classification criteria were developed in the following four phases.
The accuracy for each class in the validation set is shown below.
| Uveitis Class | Accuracy (%) | 95% Confidence Interval |
|---|---|---|
| Anterior segment (9 diseases) | 96.7 | 92.4–98.6 |
| Intermediate segment (5 diseases) | 99.3 | 96.1–99.9 |
| Posterior (9 diseases) | 98.0 | 94.3–99.3 |
Panuveitis (7 diseases) was 94.0% (89.0–96.8). Infectious posterior/panuveitis (5 diseases) was 93.3% (89.1–96.3). Accuracy of 93% or higher was achieved in all classes.
In the SUN II classification, exclusion criteria are set for each disease. The following are commonly used exclusion items across diseases.
The SUN II classification criteria were developed for research purposes and have several limitations when directly applied in clinical settings.
In Japanese ophthalmology practice, uveitis has been classified along three axes: site, etiology, and nature. Sarcoidosis, Behçet’s disease, and Vogt-Koyanagi-Harada disease, which are common in Japan, are all included in the SUN II classification criteria.
The SUN grading system is used as the global standard for evaluating anterior chamber inflammation. It assesses inflammatory cells observed within a 1×1 mm slit-lamp beam field in six grades (0 to 4+).
The SUN II classification criteria are an international research classification and are used in Japan to define patient populations in clinical studies. However, in daily practice, comprehensive diagnosis based on conventional clinical findings and various tests takes priority.
The SUN II classification criteria are designed to reflect the pathophysiological features of each disease. The rationale for classification by major etiology is shown below.
In the classification of infectious uveitis, identification of the pathogen is central. PCR testing of aqueous humor or vitreous fluid plays an important role.
A definitive diagnosis of the systemic disease is a prerequisite.
Exclusion of systemic diseases and infections is a prerequisite. In Fuchs uveitis syndrome, heterochromia iridis and stellate keratic precipitates are characteristic findings. Birdshot retinochoroiditis is known to have a strong association with HLA-A29.
Anterior chamber fluid PCR testing is important mainly for differentiating viral anterior uveitis. Although not mandatory for all uveitis cases, it is useful when herpes or CMV infection is suspected. The indication should be determined based on clinical findings.
Since its publication, the SUN II classification criteria have been implemented in over 50 clinical studies1). They are widely cited, particularly in the fields of sarcoidosis-related uveitis and tuberculous uveitis.
The SUN II classification criteria were developed for research purposes, but their expansion into future clinical diagnostic criteria is being considered. Since the current classification criteria prioritize specificity, there are situations where sensitivity is insufficient.
In the field of tuberculous uveitis, it has been pointed out that the SUN criteria are more restrictive than the COTS guidelines2). In clinical practice, the COTS guidelines are considered more widely applicable, and clarifying the relationship between the two is a future challenge.
In a retrospective study of 166 pediatric uveitis cases, anterior uveitis was the most common at 75.3%3). In juvenile idiopathic arthritis-associated uveitis, anterior uveitis accounted for 97.8%, with complications including cataract (9.3%), elevated intraocular pressure (11%), and posterior synechiae (19.5%). Accumulation of pediatric data based on the SUN classification is progressing.
