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What is Uveitis and explain in detail?
Uveitis () is the inflammation of the uvea, the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is described anatomically, by the part of the eye affected, as anterior, intermediate or posterior, from front to back. In the panuveitic form, all parts are involved. The most common form is the anterior one. Symptoms include pain, floaters and blurred vision, and clinical examination may show redness and an irregular pupil, while ophthalmic examination shows dilated ciliary blood vessels and the presence of cells in the anterior chamber. Uveitis may arise spontaneously and associated with some genetic factors, or be associated with a wide range of conditions including autoimmune disease and infections. While the eye is a relatively protected environment, its immune mechanisms may be overcome resulting in inflammation and tissue destruction associated with T-cell activation. The incidence is approximately 1:4500, most commonly between the ages of 20–60.
Uveitis is an ophthalmic emergency and requires a thorough examination by an ophthalmologist or optometrist, including dilation of the pupil to allow better visualisation. Urgent treatment is required to control the inflammation. Further procedures may be required to identify any underlying disease. Treatment usually involves the use of steroids, most commonly as eye drops. Any underlying disease, for instance herpes zoster (shingles) will also require treatment. While initial treatment is usually successful, complications include other ocular disorders, such as uveitic glaucoma, retinal detachment, optic nerve damage, cataracts, and in some cases, a permanent loss of vision. In the United States uveitis accounts for about 10%-20% of cases of blindness.

Signs and symptoms
The signs and symptoms of uveitis include the following;

Anterior uveitis (Iritis)
Pain in the eye(s)
Redness of the eye(s)
Blurred vision
Photophobia
Irregular pupil
Signs of anterior uveitis include dilated ciliary vessels, presence of cells and flare in the anterior chamber, and keratic precipitates ("KP") on the posterior surface of the cornea. In severe inflammation there may be evidence of a hypopyon. Old episodes of uveitis are identified by pigment deposits on lens, KPs, and festooned pupil on dilation of pupil.
Busacca nodules, inflammatory nodules located on the surface of the iris in granulomatous forms of anterior uveitis such as Fuchs heterochromic iridocyclitis (FHI).
Synechia

Intermediate uveitis
Most common:

Floaters, which are dark spots that float in the visual field
Blurred visionIntermediate uveitis usually affects one eye. Less common is the presence of pain and photophobia.

Posterior uveitis
Inflammation in the back of the eye is commonly characterized by:

Floaters
Blurred vision

Causes
Uveitis is usually an isolated illness, but can be associated with many other medical conditions. In anterior uveitis, no associated condition or syndrome is found in approximately one-half of cases. However, anterior uveitis is often one of the syndromes associated with HLA-B27. Presence of this type of HLA allele has a relative risk of evolving this disease by approximately 15%.The most common form of uveitis is acute anterior uveitis (AAU). It is most commonly associated with HLA-B27, which has important features: HLA-B27 AAU can be associated with ocular inflammation alone or in association with systemic disease. HLA-B27 AAU has characteristic clinical features including male preponderance, unilateral alternating acute onset, a non-granulomatous appearance, and frequent recurrences, whereas HLA-B27 negative AAU has an equivalent male to female onset, bilateral chronic course, and more frequent granulomatous appearance. Rheumatoid arthritis is not uncommon in Asian countries as a significant association of uveitis.

Noninfectious or autoimmune causes
Sympathetic ophthalmia
Behçet disease
Crohns disease
Fuchs heterochromic iridocyclitis
Granulomatosis with polyangiitis
HLA-B27 related uveitis
Spondyloarthritis (especially seen in ankylosing spondylitis)
Juvenile idiopathic arthritis
Sarcoidosis
Tubulointerstitial nephritis and uveitis syndrome

Infectious causes
Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:

brucellosis
herpesviruses (herpes zoster ophthalmicus - shingles of the eye)
leptospirosis
Lyme disease
presumed ocular histoplasmosis syndrome
syphilis
toxocariasis
toxoplasmic chorioretinitis
tuberculosis
Zika fever

Associated with systemic diseases
Systemic disorders that can be associated with uveitis include:
Enthesitis
Ankylosing spondylitis
Juvenile rheumatoid arthritis
psoriatic arthritis
reactive arthritis
Behçets disease
inflammatory bowel disease
Whipples disease
systemic lupus erythematosus
polyarteritis nodosa
Kawasakis disease
chronic granulomatous disease
sarcoidosis
multiple sclerosis
Vogt–Koyanagi–Harada disease

Drug related side effects
Rifabutin, a derivative of Rifampin, has been shown to cause uveitis.
Several reports suggest the use of quinolones, especially Moxifloxacin, may lead to uveitis.

White Dot syndromes
Occasionally, uveitis is not associated with a systemic condition: the inflammation is confined to the eye and has unknown cause. In some of these cases, the presentation in the eye is characteristic of a described syndrome, which are called white dot syndromes, and include the following diagnoses:

acute posterior multifocal placoid pigment epitheliopathy
birdshot chorioretinopathy
multifocal choroiditis and panuveitis
multiple evanescent white dot syndrome
punctate inner choroiditis
serpiginous choroiditis
acute zonal occult outer retinopathy

Masquerade syndromes
Masquerade syndromes are those conditions that include the presence of intraocular cells but are not due to immune-mediated uveitis entities. These may be divided into neoplastic and non-neoplastic conditions.

Non-neoplastic:retinitis pigmentosa
intraocular foreign body
juvenile xanthogranuloma
retinal detachmentNeoplastic:retinoblastoma
lymphoma
malignant melanoma
leukemia
reticulum cell sarcoma

Pathophysiology
Immunologic factors
Onset of uveitis can broadly be described as a failure of the ocular immune system and the disease results from inflammation and tissue destruction. Uveitis is driven by the Th17 T cell sub-population that bear T-cell receptors specific for proteins found in the eye. These are often not deleted centrally whether due to ocular antigen not being presented in the thymus (therefore not negatively selected) or a state of anergy is induced to prevent self targeting.Autoreactive T cells must normally be held in check by the suppressive environment produced by microglia and dendritic cells in the eye. These cells produce large amounts of TGF beta and other suppressive cytokines, including IL-10, to prevent damage to the eye by reducing inflammation and causing T cells to differentiate to inducible T reg cells. Innate immune stimulation by bacteria and cellular stress is normally suppressed by myeloid suppression while inducible Treg cells prevent activation and clonal expansion of the autoreactive Th1 and Th17 cells that possess potential to cause damage to the eye.
Whether through infection or other causes, this balance can be upset and autoreactive T cells allowed to proliferate and migrate to the eye. Upon entry to the eye, these cells may be returned to an inducible Treg state by the presence of IL-10 and TGF-beta from microglia. Failure of this mechanism leads to neutrophil and other leukocyte recruitment from the peripheral blood through IL-17 secretion. Tissue destruction is mediated by non-specific macrophage activation and the resulting cytokine cascades. Serum TNF-α is significantly elevated in cases while IL-6 and IL-8 are present in significantly higher quantities in the aqueous humour in patients with both quiescent and active uveitis. These are inflammatory markers that non-specifically activate local macrophages causing tissue damage.

Genetic factors
The cause of non-infectious uveitis is unknown but there are some strong genetic factors that predispose disease onset including HLA-B27 and the PTPN22 genotype.

Infectious agents
Recent evidence has pointed to reactivation of herpes simplex, varicella zoster and other viruses as important causes of developing what was previously described as idiopathic anterior uveitis. Bacterial infection is another significant contributing factor in developing uveitis.

Diagnosis
Diagnosis includes dilated fundus examination to rule out posterior uveitis, which presents with white spots across the retina along with retinitis and vasculitis.
Laboratory testing is usually used to diagnose specific underlying diseases, including rheumatologic tests (e.g. antinuclear antibody, rheumatoid factor) and serology for infectious diseases (Syphilis, Toxoplasmosis, Tuberculosis).
Major histocompatibility antigen testing may be performed to investigate genetic susceptibility to uveitis. The most common antigens include HLA-B27, HLA-A29 (in birdshot chorioretinopathy) and HLA-B51 (in Behçet disease).Radiology X-ray may be used to show coexisting arthritis and chest X-ray may be helpful in sarcoidosis.

Classification
Uveitis is classified anatomically into anterior, intermediate, posterior, and panuveitic forms—based on the part of the eye primarily affected. Prior to the twentieth century, uveitis was typically referred to in English as "ophthalmia."
Anterior uveitis includes iridocyclitis and iritis.  Iritis is the inflammation of the anterior chamber and iris.  Iridocyclitis is inflammation of the iris and ciliary body with inflammation predominantly confined to ciliary body.  Anywhere from two-thirds to 90% of uveitis cases are anterior in location (iritis).  This condition can occur as a single episode and subside with proper treatment or may take on a recurrent or chronic nature.
Intermediate uveitis, also known as pars planitis, consists of vitritis—which is inflammation of cells in the vitreous cavity, sometimes with snowbanking, or deposition of inflammatory material on the pars plana