Uveitis () is inflammation of the
uvea, the pigmented layer of the
eye
Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...
between the inner
retina and the outer fibrous layer composed of the
sclera
The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen and some crucial elastic fiber. In humans, and som ...
and
cornea. The uvea consists of the middle layer of pigmented
vascular structures of the eye and includes the
iris,
ciliary body, and
choroid
The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
. Uveitis is described anatomically, by the part of the eye affected, as anterior,
intermediate or posterior, or panuveitic if all parts are involved. Anterior uveitis (
iridocyclytis) is the most common, with the incidence of uveitis overall affecting approximately 1:4500, most commonly those between the ages of 20-60. Symptoms include eye pain, eye redness,
floaters and blurred vision, and ophthalmic examination may show dilated
ciliary blood vessels and the presence of cells in the
anterior chamber. Uveitis may arise spontaneously, have a genetic component, or be associated with an
autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
or
infection. 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.
Uveitis is an ophthalmic emergency that requires urgent control of the inflammation to prevent vision loss. Treatment typically involves the use of topical eye drop
steroids
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
,
intravitreal injection, newer
biologics, and treating any underlying disease. While initial treatment is usually successful, complications include other ocular disorders, such as
uveitic glaucoma,
retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...
,
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.
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. 66% - 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
Vitreous may refer to:
Materials
* Glass, an amorphous solid material
** Vitreous enamel, a material made by fusing powdered glass to a substrate by firing
* Vitreous lustre, a glassy luster or sheen on a mineral surface
Biology
* Vitreous body, ...
cavity, sometimes with ''snowbanking'', or deposition of inflammatory material on the
pars plana. There are also "snowballs," which are inflammatory cells in the vitreous.
* Posterior uveitis or
chorioretinitis is the inflammation of the
retina and
choroid
The choroid, also known as the choroidea or choroid coat, is a part of the uvea, the vascular layer of the eye, and contains connective tissues, and lies between the retina and the sclera. The human choroid is thickest at the far extreme rear ...
.
* Pan-uveitis is the inflammation of all layers of the uvea(Iris, ciliary body and choroid).
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
The relative risk (RR) or risk ratio is the ratio of the probability of an outcome in an exposed group to the probability of an outcome in an unexposed group. Together with risk difference and odds ratio, relative risk measures the association bet ...
of evolving this disease by approximately 15%.
[Table 5-7 in: ]
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 Behçet is a Turkish name and may refer to:
Given name
* Behçet Cantürk, Turkish mob boss
* Behçet Necatigil, Turkish author and poet
* Behçet Uz, Turkish politician and doctor
Surname
* Hulusi Behçet, Turkish dermatologist and scientist
Ot ...
*
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...
*
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
*
Associated with systemic diseases
Systemic disorders that can be associated with uveitis include:
*
Enthesitis
Enthesitis is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. It is an enthesopathy, a pathologic condition of the entheses. Early clinical manifestations are an aching sensation akin to "working out too ...
*
Ankylosing spondylitis
*
Juvenile rheumatoid arthritis
*
psoriatic arthritis
*
reactive arthritis
*
Behçet's disease
*
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
*
Whipple's disease
*
systemic lupus erythematosus
Lupus, technically known as systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Comm ...
*
polyarteritis nodosa
*
Kawasaki's disease
Kawasaki disease is a syndrome of unknown cause that results in a fever and mainly affects children under 5 years of age. It is a form of vasculitis, where blood vessels become inflamed throughout the body. The fever typically lasts for more tha ...
*
chronic granulomatous disease
*
sarcoidosis
*
multiple sclerosis
Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...
*
Vogt–Koyanagi–Harada disease
Infectious causes
Uveitis may be an immune response to fight an infection caused by an organism in the eye. They are less common than non-infectious causes, and require antimicrobial/ viral/ parasitic treatment in addition to inflammatory control. Infectious causes in order of global burden include:
*
tuberculosis
*
brucellosis
* herpesviruses (
herpes zoster ophthalmicus -
shingles
Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
of the eye)
*
leptospirosis
Leptospirosis is a blood infection caused by the bacteria ''Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, severe ...
*
presumed ocular histoplasmosis syndrome
*
syphilis
Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, an ...
*
toxocariasis
*
toxoplasmic chorioretinitis
*
Lyme disease
*
Zika fever
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 White dot syndromes are inflammatory diseases characterized by the presence of white dots on the fundus (eye), fundus, the interior surface of the eye.[acute posterior multifocal placoid pigment epitheliopathy
Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an acquired inflammatory uveitis that belongs to the heterogenous group of white dot syndromes in which light-coloured (yellowish-white) lesions begin to form in the macular ar ...](_blank ...<br></span></div>, and include the following diagnoses:
*<div class=)
*
birdshot chorioretinopathy
Birdshot chorioretinopathy, now commonly named birdshot uveitis or HLA-A29 uveitis, is a rare form of bilateral posterior uveitis affecting both eyes. It causes severe, progressive inflammation of both the choroid and retina.
Affected individuals ...
*
multifocal choroiditis and panuveitis
*
multiple evanescent white dot syndrome
Multiple evanescent white dot syndrome (MEWDS) is an uncommon inflammatory condition of the retina that typically affects otherwise healthy young females in the second to fourth decades of life.
The typical patient with MEWDS is a healthy middl ...
*
punctate inner choroiditis
Punctate inner choroiditis (PIC) is an inflammatory choroiditis which occurs mainly in young women. Symptoms include blurred vision and scotomata. Yellow lesions are mainly present in the posterior pole and are between 100 and 300 micrometres in ...
*
serpiginous choroiditis
*
acute zonal occult outer retinopathy
Acute zonal occult outer retinopathy (AZOOR) is an inflammatory retinopathy in the category of white dot syndromes typified by acute loss of one or more zones of outer retinal function associated with photopsia, minimal funduscopic changes and abno ...
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
Juvenile xanthogranuloma is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".
It is a rare skin disorder that primarily affects children under one year of age but can also be found in olde ...
:*
retinal detachment
Retinal detachment is a disorder of the eye in which the retina peels away from its underlying layer of support tissue. Initial detachment may be localized, but without rapid treatment the entire retina may detach, leading to vision loss and blin ...
*Neoplastic:
:*
retinoblastoma
:*
lymphoma
:*
malignant melanoma
:*
leukemia
:*
reticulum cell sarcoma
A sarcoma is a malignant tumor, a type of cancer that arises from transformed cells of mesenchymal ( connective tissue) origin. Connective tissue is a broad term that includes bone, cartilage, fat, vascular, or hematopoietic tissues, and sarc ...
Signs and symptoms
The disease course, anatomy, and laterality can vary widely and are important to consider in diagnosis and treatment. Cases may be acute (sudden onset with < 3 month duration) and monophonic, acute and recurrent, or chronic. The signs and symptoms of uveitis may include the following;
Anterior uveitis (Iritis)
* Pain in the eye(s)
* Redness of the eye(s)
*
Blurred vision
Blurred vision is an ocular symptom where vision becomes less precise and there is added difficulty to resolve fine details.
Temporary blurred vision may involve dry eyes, eye infections, alcohol poisoning, hypoglycemia, or low blood pressure. ...
*
Photophobia
* Irregular pupil
* Signs of anterior uveitis include dilated
ciliary vessels, presence of cells and flare in the anterior chamber, and
keratic precipitate
Keratic precipitate (KP) is an inflammatory cellular deposit seen on corneal endothelium. Acute KPs are white and round in shape whereas old KPs are faded and irregular in shape. Mutton-fat KPs are large in shape and are greasy-white in color an ...
s ("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, adhesion of the iris to the cornea (anterior synechiae) or more commonly the lens (posterior synechiae)
Intermediate uveitis
Most common:
*
Floaters, which are dark spots that float in the visual field
* Blurred vision
Intermediate 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
Pathophysiology
Immunologic factors
Onset of uveitis can broadly be described as a failure of the
ocular immune system
The ocular immune system protects the eye from infection and regulates healing processes following injuries. The interior of the eye lacks lymph vessels but is highly vascularized, and many immune cells reside in the uvea, including mostly macropha ...
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
Microglia are a type of neuroglia (glial cell) located throughout the brain and spinal cord. Microglia account for about 7% of cells found within the brain. As the resident macrophage cells, they act as the first and main form of active immune de ...
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
White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...
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
The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posterio ...
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
On exam an ophthalmologist will be able to tell if uveitis is active or inactive.
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.
Treatment
Uveitis is typically treated with
glucocorticoid steroid
A steroid is a biologically active organic compound with four rings arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter membrane fluidity; and a ...
s, either as topical eye drops (prednisolone acetate) or as oral therapy. Prior to the administration of corticosteroids,
corneal ulcers must be ruled out. This is typically done using a fluorescence dye test. In addition to corticosteroids, topical
cycloplegics, such as
atropine
Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
or
homatropine, may be used. Successful treatment of active uveitis increases
T-regulatory cell
The regulatory T cells (Tregs or Treg cells), formerly known as suppressor T cells, are a subpopulation of T cells that modulate the immune system, maintain tolerance to self-antigens, and prevent autoimmune disease. Treg cells are immunosu ...
s in the eye, which likely contributes to disease regression.
In severe cases an injection of posterior
subtenon triamcinolone acetate may also be given to reduce the swelling of the eye.
Intravitrial injection of steroid has proven to be a newer useful way to control inflammation for longer without the need for daily eyedrops. Dexamethasone and fluocinolone acetonide are two more commonly used options for noninfectious uveitis.
Non-biologic, steroid sparing therapies for noninfectious uveitis in adults are now more available. These include the disease-modifying antirheumatic drugs (DMARDs) methotrexate, mycophenolate, cyclosporine, azathioprine, and tacrolimus.
In comparing various studies, methotrexate is more efficacious than mycophenolate in inflammatory control for most forms of panuveitis. Methotrexate also had little to no differences in safety outcomes compared to mycophenolate.
Antimetabolite medications, such as
methotrexate
Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...
are often used for recalcitrant or more aggressive cases of uveitis. Experimental treatments with
Infliximab or other anti-TNF infusions may prove helpful.
The anti-diabetic drug
metformin is reported to inhibit the process that causes the inflammation in uveitis.
In the case of herpetic uveitis, anti-viral medications, such as
valaciclovir or
aciclovir, may be administered to treat the causative viral infection.
Epidemiology
Uveitis affects approximately 1 in 4500 people and is most common between the ages 20 to 60 with men and women affected equally. In western countries, anterior uveitis accounts for between 50% and 90% of uveitis cases. In Asian countries the proportion is between 28% and 50%. Uveitis is estimated to be responsible for approximately 10%-20% of the blindness in the United States.
For non-infectious uveitis, women are more likely (57%) to be affected than men, possibly due to their higher prevalence of related
autoimmune disease
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
s.
Vitamin D deficiency and smoking are risk factors for non-infectious uveitis.
[
]
Prognosis
The prognosis is generally good for those who receive prompt diagnosis and treatment, but serious complication including cataracts, uveitic glaucoma, band keratopathy, macular edema and permanent vision loss may result if left untreated. The type of uveitis, as well as its severity, duration, and responsiveness to treatment or any associated illnesses, all factor into the outlook.
Research
See also
* List of systemic diseases with ocular manifestations
* Intermediate uveitis
* Uveitis–Glaucoma–Hyphema syndrome
References
Bibliography
*
*
{{Authority control
Inflammations
Disorders of iris and ciliary body
Steroid-responsive inflammatory conditions