Patofisiologi uveitis intermediet

There may be an immunogenetic predisposition for the disorder in some

cases (see Causes), accounting for family clustering that is seen on occasion,
indicating environmental or hereditary associations. The available evidence
would suggest an autoimmune mechanism; however, the antigenic stimulus
remains elusive

Epidemiology
Frequency
United States
Traditionally, the proportion of patients with intermediate uveitis is estimated
to be 4-8% of uveitis cases in referral centers. The National Institutes of
Health (NIH) reports a higher percentage (15%), which may indicate improved
awareness or the nature of the uveitis referral clinic. In the pediatric
population, intermediate uveitis can account for up to 25% of uveitis cases.
Mortality/Morbidity
Permanent loss of vision is most commonly seen in patients with chronic
cystoid macular edema (CME). Every effort must be made to eradicate CME
when present. Other less common causes of visual loss include
rhegmatogenous retinal detachment, glaucoma, band keratopathy, cataracts,
vitreous hemorrhage, epiretinal membrane, and choroidal neovascularization.
Race
No racial predilection exists for this disease.
Sex
The incidence of intermediate uveitis is equal in men and women.
Age
Although intermediate uveitis can develop at any age, it primarily afflicts
children and young adults. There is a bimodal distribution with one peak in the
second decade and another peak in the third or fourth decade.
In the pediatric age group, intermediate uveitis is associated with a worse
presenting visual acuity. Poorer outcomes may be related to delayed
presentation/diagnosis, the inherent difficulties of immunosuppression in
children, or a more aggressive disease
Symptoms
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.

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.
The presenting visual acuity is often reduced to 20/40 (mild visual loss) due to mild
vitritis and CME.
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.
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.
o In severe cases, the exudates may coalesce across the entire periphery for
360, albeit rarely.
o 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.
o In fact, snowbanks may be fibroglial masses and not a true protein exudate
(see Histologic Findings).
Peripheral retinal vascular abnormalities are not uncommon but may become
obscured by the dense vitritis.
o Sheathing or obliteration of small venules may be noted. This finding may
appear months or years after initial presentation.
o Less often, a periarteritis or a combined perivasculitis is present with
exudates.
o Peripheral retinal neovascularization can occur as a result of ischemia,
causing vitreous hemorrhages; this occurs more commonly in children.
o 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.
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.
o Estimates of the incidence of macular edema vary.
 o Most early reports have noted this complication in 28-50% of cases.
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.
In the anterior segment, late findings include anterior and posterior synechiae,
band keratopathy, cataracts, and glaucoma.
o The glaucoma may be related to both the uveitis and/or corticosteroid use.
o 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.
The late complications of intermediate uveitis are important to recognize early.
o 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.
o Chronic CME may cause moderate-to-severe vision loss. Treating CME,
regardless of how good the vision may be, is therefore imperative.
o Peripheral retinal neovascularization can occur as a result of ischemia,
causing vitreous hemorrhages, as discussed above.
o 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 anatomical
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.
In 1963, Kimura and Hogan first noted several members of one family to
be afflicted with chronic cyclitis. [1] Since then, there have been multiple
case reports of intermediate uveitis in families, including a case report in
identical twins.
o 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.
o 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. [2] 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.
o Other associations include HLA-A28, HLA-B8, and HLA-B51.
o It is evident that genetics plays some role in the pathophysiology of
intermediate uveitis, but the importance remains unclear.
o 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 of disease
development and may also run a more severe course.
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.
o 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 his colleagues. [2, 3]
o 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.

Imaging Studies
Fluorescein angiography
Fluorescein angiography is useful in determining the presence and extent of
CME.
Knowing if CME exists helps in choosing the appropriate treatment plan.
The angiogram provides information about the integrity of the retinal
vasculature. Staining of the vessel walls and/or leakage indicates a
perivasculitis.
Retinal neovascularization and optic nerve edema can be recognized easily.
B-scan ultrasonography
When media are obscured by vitreous hemorrhage, inflammatory debris,
cyclitic membrane, or cataract, B-scan ultrasonography can be useful.
Obtain B-scan ultrasonography to document the extent of vitreous debris,
retinal detachment, and cyclitic membranes.
Ultrasound biomicroscopy may show features that are not clinically obvious,
such as uveal thickening, the exact nature of inflammatory condensations in
the vitreous, and vitreoretinal adhesions with traction.
Both 50 MHz and 20 MHz ultrasound imaging in patients with intermediate
uveitis readily demonstrated inferior pars plana exudates and cyclitic bands,
which are of extreme value in preoperative planning in patients with dense
media and/or a secluded pupil due to posterior synechiae.

Optical coherence tomography (OCT)

OCT has replaced traditional fluorescein angiography as the imaging modality of choice
in establishing a diagnosis of CME.
OCT can help demonstrate the presence of cysts in the fovea and measure macular
thickness. OCT is a highly sensitive, noninvasive method to help diagnose CME and
provides the best method to monitor the therapeutic response of patients to treatment
as macular thickness appears to correlate with visual acuity to some degree.
OCT can also help demonstrate the presence of epiretinal membranes, a known late
complication of ocular inflammation.
The presence of neurologic symptoms or a history of optic neuritis should prompt the
clinician to obtain an MRI of the brain and subsequent consultation with a neurologist to
rule out MS.
If there is a high clinical suspicion of sarcoidosis as the cause of intermediate uveitis, a
chest X-ray or a Gallium scan should be obtained as indicated. Older women with a
negative chest X-ray and ACE may have hilar adenopathy identified on chest CT.

Histologic Findings
Histologic examination of the pars plana snowbank shows that it is not a true
protein exudate. The snowbanks are predominantly a combination of
collapsed vitreous, blood vessels, inflammatory cells (mainly lymphocytes),
fibroblasts, and glial elements. Histologic studies also failed to identify cells
positive for GFAP, an important glial cell marker, within the snowbanks.
Peripheral veins may manifest lymphocytic infiltration and cuffing. The
vascular component of the snowbanks has been shown to be continuous with
retinal vessels. Vitreous snowballs are composed of epithelioid cells and
multinucleated giant cells.