Uveitis
Dr. Abhishek Onkar
 Uveitis is defined as inflammation of
the uveal tract, which includes the iris,
ciliary body, and choroid.
 Anterior uveitis, the most common
form, includes iritis; iridocyclitis, in
which the ciliary body is also involved;
and anterior cyclitis.
 Uveitis is often idiopathic (upto 50%),
but it can be triggered by genetic,
traumatic, or infectious mechanisms.
Classification
Anatomical classification
After anatomical classification, uveitis is
further described by the following :
 Onset (sudden vs insidious)
 Duration (limited—less than 3 months in
duration, or persistent—greater than 3
months in duration)
 Course (acute, recurrent, or chronic)
 Laterality (unilateral vs bilateral)
 Aetiological: infectious, non-infectious,
idiopathic
 Pathological: granulomatous, non-
granulomatous
Infectious and non-infectious
causes of uveitis
Acute anterior uveitis presents as follows :
 Pain, generally developing over a few
hours or days except in cases of trauma
 Redness
 Photophobia
 Excessive tearing
 Decreased vision
 Chronic anterior uveitis presents
primarily as blurred vision and mild
redness. Patients have little pain or
photophobia except when having an
acute episode.
Posterior uveitis presents as follows :
 Blurred vision and floaters
 Absence of symptoms of anterior uveitis
(ie, pain, redness, and photophobia)
 The presence of symptoms of posterior
uveitis and pain suggests one of the
following:
 Anterior chamber involvement
 Bacterial endophthalmitis
 Posterior scleritis
Intermediate uveitis presents as
follows :
 Painless floaters and decreased vision
(similar to posterior uveitis)
 Minimal photophobia or external
inflammation
 Patients with panuveitis may present
with any or all of the above symptoms.
Pathophysiology
 The etiology of uveitis is often idiopathic.
 However, genetic, traumatic, or infectious
mechanisms are known to promote or trigger
uveitis.
 The mechanism for trauma is believed to be a
combination of microbial contamination and
accumulation of necrotic products at the site of
injury, thereby stimulating proinflammatory
processes.
 For infectious etiologies of uveitis, it is postulated
that the immune reaction directed against foreign
molecules or antigens may injure the uveal tract
vessels and cells.
 When uveitis is found in association with
autoimmune disorders, the mechanism may be a
hypersensitivity reaction involving immune
complex deposition within the uveal tract.
Immune Mechanisms of uveitis
 The immunologic mechanisms of uveitis associated with systemic
or autoimmune diseases are multifactorial, and the exact process
remains unclear. But, known factors include genetic
susceptibility, previous exposure to infectious agents and
loss of immune privilege.
 Genetic susceptibility to immune-mediated diseases is linked to
specific human leukocyte antigen (HLA) subtypes. Human
leukocyte antigens are associated with immune responses and
play a prominent role in organ transplant rejection, vulnerability to
autoimmune diseases and susceptibility to infectious diseases.
 HLA molecules are proteins (peptides) that are present on the
surfaces of many cells of the body. They represent the product of
genes comprising the major histocompatibility complex (MHC) on
chromosome 6. Human leukocyte antigens function to present
antigen to lymphocytes.
 Lymphocytes, in turn, recognize the HLA proteins of other cells,
determining self vs. non-self, or foreign cells. So, the HLA system
helps regulate the nature and strength of immune responses.
Mechanisms linking HLA-B27 and its associated
inflammatory diseases:
 Molecular mimicry, the resemblance of
antigenic microbial proteins to host (self) tissue.
An immune response against a microbial
component may cross-react with a similar host
structure. A T lymphocyte-mediated response
may occur against a self peptide found only in
joint tissue (arthritogenic peptide) or ocular
tissue (uveitogenic peptide).
 Abnormal forms of HLA-B27, which may
present microbial or self proteins to T cell
lymphocytes, triggering an immune response.
 HLA-B27 breakdown products, which may
serve as autoantigens and initiate an
autoimmune response.
Epidemiology
Incidence and prevalence:
The incidence of uveitis varies from 14 to 52.4/100,000 with
the overall prevalence around the world is up to 0.73%
Race
 Racial predisposition to uveitis is related to the patient's
underlying systemic disease.[3]
 Caucasian: HLA-B27, multiple sclerosis
 African American: Sarcoidosis, SLE
 Mediterranean/Middle Eastern: Behçet's disease
 Asian: Behçet's disease
Sex
 In general, uveitis does not have a gender predisposition
except in cases secondary to systemic disease, such as JRA
and SLE.
Age
 The majority of patients are aged 20-50 years.
Physical examination findings
 The lids, lashes, and lacrimal ducts are normal
 The conjunctival examination reveals 360-degree
perilimbal injection, which increases in intensity
as it approaches the limbus; this is the reverse of
the pattern seen in conjunctivitis, in which the
most severe inflammation occurs at a distance
from the limbus
 Visual acuity may be decreased in the affected
eye
 Extraocular movement generally is normal
 On the pupillary examination, the patient may
have photophobia i.e. abnormal sensitivity to
ambient light.
Slit-lamp examination
 Keratitic precipitates/ K.P.(white blood cells) on the endothelium are a
hallmark of iritis
 The typical distribution of KPs occurs in the inferior half of the cornea as a
triangle with an inferior base (Arlt's triangle)
 Small to medium keratitic precipitates are classified as non-
granulomatous, whereas granulomatous keratitic precipitates are large
and have a greasy or "mutton-fat" granular appearance.
 White or red blood Cells may be observed in the anterior chamber and
are graded on a scale of 1+ to 4+. Presence of cells in anterior chamber is
a/w active uveitis.
 an increase in the protein content of the aqueous causes an effect upon
examination known as Flare, which is similar to that produced by a
moving projector beam in a dark smoky room.
 Layered leucocytes in the anterior chamber is termed as Hypopyon.
 Adhesions between iris and peripheral cornea(peripheral anterior
synechiae) or lens(posterior synechiae) may be seen.
 Intraocular pressure may be normal or slightly decreased in the acute
phase due to decreased aqueous humor production; however, pressure
may become elevated as the inflammation subsides
 Opacities of the lens (posterior subcapsular/ complicated cataracts) may
be present but are not specific for uveitis
Differential Diagnoses
 Conjunctivitis
 Corneal Abrasion
 Corneal Ulceration and Ulcerative
Keratitis
 Foreign Body, Intraocular
 Glaucoma, Acute Angle-Closure
 Scleritis
 Ultraviolet Keratitis
Laboratory work-up
A nonspecific workup is indicated if the history and the
physical examination findings are unremarkable in the
presence of uveitis that is bilateral, granulomatous, or
recurrent. These tests, which may be ordered by the
consulting ophthalmologist, include the following :
 CBC
 Erythrocyte sedimentation rate (ESR)
 Antinuclear antibody (ANA)
 Rapid plasma reagin (RPR)
 Venereal disease research laboratory (VDRL)
 Purified protein derivative (PPD)
 Lyme titer
 HLA-B27
 Chest radiography (to assess for sarcoidosis or
tuberculosis)
Treatment
 The goals of pharmacotherapy are to
reduce pain and inflammation through
the use of cycloplegics and
corticosteroids.
 Topical Corticosteroid eye drops have
been the standard of care for uveitis.
Commonly used steroids are:
 Prednisolone 1%
 Dexamethasone 0.1%
 Loteprednol 0.5%
 Fluorometholone 0.1%
 Difluprednate 0.05%
Cycloplegic agents
Sequelae
 Peripheral anterior synechiae
 Posterior synechiae
 Total posterior synechiae
 Festooned pupil
 Seclussio pupillae/ Ring/Annular synechiae
 Iris bombe
 Secondary angle closure glaucoma
 Occlusio pupillae/cyclitic membranes
 Ectropion uvea
 Ciliary body atrophy/shutdown
 Retinal detachment
 RPE destruction
Complications
 Complicated Cataract(polychromatic
lusture, bread-crumb appearance)
 Glaucoma
 Hypotony (Phthisis bulbi)
 Cystoid macular edema
 Band shaped keratopathy
Prognosis
 Generally, the prognosis for iritis and
uveitis is good with appropriate
treatment.

Uveitis basics for undergrads

  • 1.
  • 2.
     Uveitis isdefined as inflammation of the uveal tract, which includes the iris, ciliary body, and choroid.  Anterior uveitis, the most common form, includes iritis; iridocyclitis, in which the ciliary body is also involved; and anterior cyclitis.  Uveitis is often idiopathic (upto 50%), but it can be triggered by genetic, traumatic, or infectious mechanisms.
  • 3.
  • 4.
  • 5.
    After anatomical classification,uveitis is further described by the following :  Onset (sudden vs insidious)  Duration (limited—less than 3 months in duration, or persistent—greater than 3 months in duration)  Course (acute, recurrent, or chronic)  Laterality (unilateral vs bilateral)  Aetiological: infectious, non-infectious, idiopathic  Pathological: granulomatous, non- granulomatous
  • 6.
  • 7.
    Acute anterior uveitispresents as follows :  Pain, generally developing over a few hours or days except in cases of trauma  Redness  Photophobia  Excessive tearing  Decreased vision  Chronic anterior uveitis presents primarily as blurred vision and mild redness. Patients have little pain or photophobia except when having an acute episode.
  • 8.
    Posterior uveitis presentsas follows :  Blurred vision and floaters  Absence of symptoms of anterior uveitis (ie, pain, redness, and photophobia)  The presence of symptoms of posterior uveitis and pain suggests one of the following:  Anterior chamber involvement  Bacterial endophthalmitis  Posterior scleritis
  • 9.
    Intermediate uveitis presentsas follows :  Painless floaters and decreased vision (similar to posterior uveitis)  Minimal photophobia or external inflammation  Patients with panuveitis may present with any or all of the above symptoms.
  • 10.
    Pathophysiology  The etiologyof uveitis is often idiopathic.  However, genetic, traumatic, or infectious mechanisms are known to promote or trigger uveitis.  The mechanism for trauma is believed to be a combination of microbial contamination and accumulation of necrotic products at the site of injury, thereby stimulating proinflammatory processes.  For infectious etiologies of uveitis, it is postulated that the immune reaction directed against foreign molecules or antigens may injure the uveal tract vessels and cells.  When uveitis is found in association with autoimmune disorders, the mechanism may be a hypersensitivity reaction involving immune complex deposition within the uveal tract.
  • 11.
    Immune Mechanisms ofuveitis  The immunologic mechanisms of uveitis associated with systemic or autoimmune diseases are multifactorial, and the exact process remains unclear. But, known factors include genetic susceptibility, previous exposure to infectious agents and loss of immune privilege.  Genetic susceptibility to immune-mediated diseases is linked to specific human leukocyte antigen (HLA) subtypes. Human leukocyte antigens are associated with immune responses and play a prominent role in organ transplant rejection, vulnerability to autoimmune diseases and susceptibility to infectious diseases.  HLA molecules are proteins (peptides) that are present on the surfaces of many cells of the body. They represent the product of genes comprising the major histocompatibility complex (MHC) on chromosome 6. Human leukocyte antigens function to present antigen to lymphocytes.  Lymphocytes, in turn, recognize the HLA proteins of other cells, determining self vs. non-self, or foreign cells. So, the HLA system helps regulate the nature and strength of immune responses.
  • 13.
    Mechanisms linking HLA-B27and its associated inflammatory diseases:  Molecular mimicry, the resemblance of antigenic microbial proteins to host (self) tissue. An immune response against a microbial component may cross-react with a similar host structure. A T lymphocyte-mediated response may occur against a self peptide found only in joint tissue (arthritogenic peptide) or ocular tissue (uveitogenic peptide).  Abnormal forms of HLA-B27, which may present microbial or self proteins to T cell lymphocytes, triggering an immune response.  HLA-B27 breakdown products, which may serve as autoantigens and initiate an autoimmune response.
  • 15.
    Epidemiology Incidence and prevalence: Theincidence of uveitis varies from 14 to 52.4/100,000 with the overall prevalence around the world is up to 0.73% Race  Racial predisposition to uveitis is related to the patient's underlying systemic disease.[3]  Caucasian: HLA-B27, multiple sclerosis  African American: Sarcoidosis, SLE  Mediterranean/Middle Eastern: Behçet's disease  Asian: Behçet's disease Sex  In general, uveitis does not have a gender predisposition except in cases secondary to systemic disease, such as JRA and SLE. Age  The majority of patients are aged 20-50 years.
  • 16.
    Physical examination findings The lids, lashes, and lacrimal ducts are normal  The conjunctival examination reveals 360-degree perilimbal injection, which increases in intensity as it approaches the limbus; this is the reverse of the pattern seen in conjunctivitis, in which the most severe inflammation occurs at a distance from the limbus  Visual acuity may be decreased in the affected eye  Extraocular movement generally is normal  On the pupillary examination, the patient may have photophobia i.e. abnormal sensitivity to ambient light.
  • 17.
    Slit-lamp examination  Keratiticprecipitates/ K.P.(white blood cells) on the endothelium are a hallmark of iritis  The typical distribution of KPs occurs in the inferior half of the cornea as a triangle with an inferior base (Arlt's triangle)  Small to medium keratitic precipitates are classified as non- granulomatous, whereas granulomatous keratitic precipitates are large and have a greasy or "mutton-fat" granular appearance.  White or red blood Cells may be observed in the anterior chamber and are graded on a scale of 1+ to 4+. Presence of cells in anterior chamber is a/w active uveitis.  an increase in the protein content of the aqueous causes an effect upon examination known as Flare, which is similar to that produced by a moving projector beam in a dark smoky room.  Layered leucocytes in the anterior chamber is termed as Hypopyon.  Adhesions between iris and peripheral cornea(peripheral anterior synechiae) or lens(posterior synechiae) may be seen.  Intraocular pressure may be normal or slightly decreased in the acute phase due to decreased aqueous humor production; however, pressure may become elevated as the inflammation subsides  Opacities of the lens (posterior subcapsular/ complicated cataracts) may be present but are not specific for uveitis
  • 20.
    Differential Diagnoses  Conjunctivitis Corneal Abrasion  Corneal Ulceration and Ulcerative Keratitis  Foreign Body, Intraocular  Glaucoma, Acute Angle-Closure  Scleritis  Ultraviolet Keratitis
  • 21.
    Laboratory work-up A nonspecificworkup is indicated if the history and the physical examination findings are unremarkable in the presence of uveitis that is bilateral, granulomatous, or recurrent. These tests, which may be ordered by the consulting ophthalmologist, include the following :  CBC  Erythrocyte sedimentation rate (ESR)  Antinuclear antibody (ANA)  Rapid plasma reagin (RPR)  Venereal disease research laboratory (VDRL)  Purified protein derivative (PPD)  Lyme titer  HLA-B27  Chest radiography (to assess for sarcoidosis or tuberculosis)
  • 23.
    Treatment  The goalsof pharmacotherapy are to reduce pain and inflammation through the use of cycloplegics and corticosteroids.  Topical Corticosteroid eye drops have been the standard of care for uveitis. Commonly used steroids are:  Prednisolone 1%  Dexamethasone 0.1%  Loteprednol 0.5%  Fluorometholone 0.1%  Difluprednate 0.05%
  • 24.
  • 27.
    Sequelae  Peripheral anteriorsynechiae  Posterior synechiae  Total posterior synechiae  Festooned pupil  Seclussio pupillae/ Ring/Annular synechiae  Iris bombe  Secondary angle closure glaucoma  Occlusio pupillae/cyclitic membranes  Ectropion uvea  Ciliary body atrophy/shutdown  Retinal detachment  RPE destruction
  • 28.
    Complications  Complicated Cataract(polychromatic lusture,bread-crumb appearance)  Glaucoma  Hypotony (Phthisis bulbi)  Cystoid macular edema  Band shaped keratopathy
  • 29.
    Prognosis  Generally, theprognosis for iritis and uveitis is good with appropriate treatment.