History
The most common symptoms of intermediate uveitis are blurry vision and floaters.
Pain and photophobia are the exception.
Bilateral involvement at initial presentation approaches 80%, although it is frequently asymmetric. Eventually, approximately one third of unilateral cases will become bilateral.
Later in the disease course, more severe visual loss may occur secondary to chronic CME (28-50%), uveitic glaucoma (15%), rhegmatogenous retinal detachment (3-22%), vitreous hemorrhage (6-28%), cataracts (15-20%), or cyclitic membrane development.
Physical
Physical findings include the following:
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On ocular examination, the ophthalmologist encounters vitritis that ranges in severity. The absence of cellular activity in the vitreous precludes the diagnosis of active intermediate uveitis.
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The presenting visual acuity is often reduced to 20/40 (mild visual loss) due to mild vitritis and CME.
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Anterior segment inflammation is infrequent and more commonly associated with pediatric intermediate uveitis. On occasion, patients with MS develop granulomatous anterior uveitis with characteristic mutton keratic precipitates.
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Aggregates of inflammatory cells may appear in the inferior vitreous as white or yellow tufts termed vitreous snowballs. A snowbank, the requisite finding in pars planitis, may be seen as a grayish yellow exudate along the inferior ora serrata, frequently extending over the pars plana. Not all patients with intermediate uveitis manifest snowbanks.
In severe cases, the exudates may coalesce across the entire periphery for 360°, albeit rarely.
Scleral depression is usually required to appreciate snowbanks, but, sometimes, they can be seen with the eye infraducted using an indirect ophthalmoscope without the 20 D-lens.
In fact, snowbanks may be fibroglial masses and not a true protein exudate (see Histologic Findings).
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Peripheral retinal vascular abnormalities are not uncommon but may become obscured by the dense vitritis.
Sheathing or obliteration of small venules may be noted. This finding may appear months or years after initial presentation.
Less often, a periarteritis or a combined perivasculitis is present with exudates.
Peripheral retinal neovascularization can occur as a result of ischemia, causing vitreous hemorrhages; this occurs more commonly in children.
The neovascularization can evolve into a vascular cyclitic membrane in the rare patient, exercising traction on the ciliary body and leading to hypotony and phthisis bulbi.
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CME may be seen. Severe macular edema can be appreciated clinically. Angiographic study or optical coherence tomography is often necessary for a definitive diagnosis, especially if the edema is subtle or if the media are hazy. Some patients with angiographic CME may present with 20/20 acuity.
Estimates of the incidence of macular edema vary.
Most early reports have noted this complication in 28-50% of cases.
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Optic nerve edema is not uncommon, especially in pediatric cases where the disk is edematous at least half of the time. In a retrospective study, optic disk edema was found in 71% of patients with onset of the disease before age 16 years.
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In the anterior segment, late findings include anterior and posterior synechiae, band keratopathy, cataracts, and glaucoma.
The glaucoma may be related to both the uveitis and/or corticosteroid use.
The incidence of cataract formation, most often a posterior subcapsular opacity, has been reported in approximately 15-20% of cases and may not be independent to the use of steroids for treatment.
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The late complications of intermediate uveitis are important to recognize early.
A combination of vitreous hemorrhage and vitreous fibrosis can cause traction on the peripheral retina and lead to retinal detachment. Studies vary widely in the frequency of this late complication, ranging from 3-22%. Some detachments may become complete, leading to a phthisical eye.
Chronic CME may cause moderate-to-severe vision loss. Treating CME, regardless of how good the vision may be, is therefore imperative.
Peripheral retinal neovascularization can occur as a result of ischemia, causing vitreous hemorrhages, as discussed above.
A vascular cyclitic membrane can exercise traction on the ciliary body and lead to hypotony and phthisis bulbi.
Causes
The cause of intermediate uveitis or pars planitis has not been elucidated. Intermediate uveitis is a category of uveitis based on an anatomic classification system that can include diseases of various etiology and clinical manifestations. Associations of the disease with such entities as MS, sarcoidosis, or inflammatory bowel disease suggest an autoimmune component in at least a subset of patients. The clustering of familial cases has led to the investigation of human leukocyte antigen (HLA) associations. The inciting event appears to be peripheral retinal perivasculitis and vascular occlusion, leading to ocular inflammation, vitritis, and snowbank formation. The etiology of the antigenic stimulus is not clear and may be either vitreal or perivascular in nature.
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In 1963, Kimura and Hogan first noted several members of one family to be afflicted with chronic cyclitis. [3] Since then, there have been multiple case reports of intermediate uveitis in families, including a case report in identical twins.
Several studies show that the HLA-DR2 histocompatibility complex gene is associated with intermediate uveitis, suggesting an immunogenetic predisposition for the disorder in some cases.
In a prospective study of 53 patients with pars planitis by Raja et al, an association was found with the HLA-DR15, a subtype of HLA-DR2. [4] In addition, there was a suggestion that the association was stronger for patients with both pars planitis and MS. This supports previous studies showing a similar relationship.
Other associations include HLA-A28, HLA-B8, and HLA-B51.
It is evident that genetics plays some role in the pathophysiology of intermediate uveitis, but the importance remains unclear.
In addition, cytokine gene polymorphism may be associated with disease development and visual prognosis in patients with intermediate uveitis. In particular, TT homozygotes for the interferon-gamma (INF-gamma) gene may be at a higher risk for disease development and may also run a more severe course.
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Despite a high prevalence of intermediate uveitis and pars planitis in uveitis clinics, the causative factors are still unknown. Apart from idiopathic forms of the disease, there are known associations with such entities as MS, sarcoidosis, and inflammatory bowel disease. Evidence of a systemic disorder can be found in up to one third of patients with intermediate uveitis. Infectious etiologies include Epstein-Barr virus (EBV) infection, Lyme disease, human T-cell lymphotrophic virus type1 (HTLV-1) infection, cat scratch disease, and hepatitis C.
The association between MS and intermediate uveitis is well documented. Raja et al reported a 16.2% prevalence rate of MS in a small population with pars planitis, which agrees with the findings of Malinowski and colleagues. [4, 5]
Retinal phlebitis, vitreous cells or snowball opacities, posterior synechiae, iritis, iridocyclitis, and retinal neovascularization are common manifestations of ocular sarcoidosis, which emphasizes the overlap of ophthalmologic signs between idiopathic intermediate uveitis and ocular sarcoidosis.
