Intermediate uveitis (IU) is a general term for intraocular inflammation primarily involving the vitreous and peripheral retina. It was defined by the Standardization of Uveitis Nomenclature (SUN) Working Group in 2005 and includes pars planitis, posterior cyclitis, and hyalitis.
In Japan, it accounts for about 1–2% of all uveitis cases, which is lower than in Western countries (around 15%). In pediatric uveitis, it can reach up to 20%. The estimated incidence is 1.4–2.0 per 100,000 people. Peak onset is reported in adults and adolescents.
The term “pars planitis” is used as a diagnosis only when the cause is unknown and snowbanks or snowballs are present (diagnosis of exclusion). Otherwise, it is called intermediate uveitis associated with an underlying disease (e.g., sarcoidosis, tuberculosis, multiple sclerosis).
Intermediate uveitis is an anatomical classification name and a general term that includes various causative diseases. Pars planitis is its idiopathic subtype, diagnosed after excluding systemic diseases. It is characterized by snowbanks and snowballs, and is common in children and young adults.
Typical symptoms begin gradually.
| Finding | Details |
|---|---|
| Snowball | Spherical yellowish-white vitreous opacity. Commonly found in the inferior periphery. Reported in up to 100% of pars planitis cases. |
| Snowbank | White fibrous inflammatory exudate on the pars plana (a dike-like exudative change from the far periphery of the retina to the pars plana). A definitive diagnostic finding for pars planitis. Relatively common in young individuals, including children. |
| Peripheral phlebitis | Appears in 16–36% of cases. Particularly common in patients with multiple sclerosis |
| Peripheral vascular sheathing | Mainly affects veins. Appears in 10–32% of cases |
| Macular edema | Main cause of vision loss. Confirmed as cystoid macular edema on optical coherence tomography (OCT) |
The incidence of visual impairment (greater than 0.3 logMAR) in pediatric intermediate uveitis is 0.05/eye-year (95% CI 0.02–0.11) 1), which is not significantly different from that of anterior uveitis (0.04/eye-year).
The main cause is macular edema (cystoid macular edema), primarily due to increased vascular permeability associated with chronic inflammation. Other causes include progression of cataracts (due to inflammation itself or steroid side effects), persistent vitreous opacities, and rarely, vitreous hemorrhage or retinal detachment.
Infectious Causes
Tuberculosis: In developing countries (e.g., India), it is a major infectious cause of intermediate uveitis. May present with snowball and snowbank findings.
Cytomegalovirus (CMV): Bilateral intermediate uveitis in immunocompetent individuals has been reported4). Diagnosis is made by PCR of aqueous humor.
Syphilis, Lyme disease, Toxocariasis, Leprosy: Consider in the differential diagnosis.
Non-infectious causes
Sarcoidosis: 2–10% of patients with intermediate uveitis have sarcoidosis. 25% of sarcoidosis patients develop intermediate uveitis. Long-term refractory cases may lead to complications such as vasoproliferative tumors 3).
Multiple sclerosis: 7–30.4% of patients with intermediate uveitis have concurrent multiple sclerosis. Retinal periphlebitis increases the risk of multiple sclerosis and optic neuritis.
Inflammatory bowel disease, tubulointerstitial nephritis and uveitis syndrome (TINU), etc.
Intermediate uveitis is a clinical diagnosis that requires exclusion of infectious diseases and systemic conditions.
Essential tests:
Ophthalmic imaging:
Fundus examination with scleral depression is essential for confirming peripheral lesions (snowballs, snowbanking).
This is indicated in the following cases:
The SUN Working Group has established the following diagnostic criteria for pars planitis:
Consider starting treatment in the following cases:
If only mild vitreous cells are present and the patient is asymptomatic, observation is possible (applicable to 25–35% of patients).
First step: Steroid therapy
Second step: immunomodulatory therapy
Added for recurrent/refractory cases, steroid-dependent cases, and cases with side effects. Cyclosporine (Neoral), methotrexate, etc. are used.
Third step: surgery/laser
When juxtapapillary choroidal neovascularization is present, effective regression has been reported with anti-VEGF therapy (e.g., intravitreal bevacizumab 1.25 mg)2). The MUST trial compared systemic therapy with fluocinolone acetonide implant and showed differences in improvement of macular thickness.
The pathology of pars planitis is thought to be a CD4+ T cell-mediated immune response to endogenous antigens. Up to 95% of total cells in the vitreous are CD4+ T cells expressing the activation marker CD69. Elevated interleukin-6 levels have been confirmed in the vitreous of patients with active intermediate uveitis, supporting the involvement of autoimmunity.
In the vitreous fluid of intermediate uveitis, compared to Fuchs heterochromic iridocyclitis, the proportion of CD4+ T cells (32.0 ± 8.6% vs 19.2 ± 8.9%) and the amount of interleukin-2 production (1810 ± 220 vs 518 ± 94 pg/ml) are significantly higher, suggesting involvement in more active inflammation and disruption of the blood-ocular barrier.
Snowballs and snowbanks are composed of a fibrovascular layer containing mononuclear leukocytes and fibroblast-like cells, along with vitreous collagen, Müller cells, and fibrous astrocytes. As chronic inflammation persists, fibrosis progresses, and the snowbank remains as a hard, snowball-like dike-shaped exudate.
Poorly controlled inflammation, peripheral vascular leakage, and hypoxic changes in the pars plana region are thought to lead to retinal elevation and the formation of vasoproliferative tumors 3). The time from uveitis diagnosis to the development of secondary vasoproliferative tumors (median) is as long as 160 months.
Association with HLA-DR2 and HLA-DR15 is observed in 67–72% of patients, suggesting a shared genetic background with multiple sclerosis and optic neuritis, which are also HLA-DR15-related diseases.
Othman et al. (2025) reported a rare case of bilateral isolated intermediate uveitis in an immunocompetent individual caused by cytomegalovirus infection 4). Cytomegalovirus was confirmed by PCR testing of aqueous humor, and the condition improved with systemic ganciclovir administration. It has been noted that cytomegalovirus intermediate uveitis presents with a morphology similar to Fuchs heterochromic iridocyclitis, making diagnosis challenging 4).
Abdel Jalil et al. (2024) reported a case of vasoproliferative tumor-induced exudative retinal detachment secondary to sarcoidosis-associated chronic intermediate uveitis 3). A combination of systemic steroids, cyclosporine, and vitrectomy (cryocoagulation plus laser photocoagulation) resulted in good visual recovery. It was again shown that pars planitis (21%) is the second most common secondary cause of vasoproliferative tumors 3).
In the MUST trial for non-infectious intermediate, posterior, and panuveitis, the fluocinolone acetonide implant showed greater improvement in macular thickness during follow-up compared to systemic therapy, and long-term data on sustained-release intraocular implants continue to accumulate.
