UVEITIS ETIOLOGY

							ETIOLOGY OF UVEITIS
Despite a great deal of experimental research and
many sophisticated methods of investigations,
etiology and immunology of the uveitis is still largely
not understood. Even today, the cause of many
clinical conditions is disputed (remains presumptive)
and in many others etiology is unknown. The
etiological concepts of uveitis as proposed by Duke
Elder, in general, are discussed here.
1. Infective uveitis. In this, inflammation of the uveal
tissue is induced by invasion of the organisms. Uveal
infections may be exogenous, secondary or
endogenous.
i Exogenous infection wherein the infecting
organisms directly gain entrance into the eye
from outside. It can occur following penetrating
injuries, perforation of corneal ulcer and postoperatively
(after intraocular operations). Such
infections usually result in an acute iridocyclitis
of suppurative (purulent) nature, which soon
turns into endophthalmitis or even
panophthalmitis.
ii Secondary infection of the uvea occurs by spread
of infection from neighbouring structures, e.g.,
acute purulent conjunctivitis. (pneumo-coccal and
gonococcal), keratitis, scleritis, retinitis, orbital
cellulitis and orbital thrombophlebitis.
iii Endogenous infections are caused by the entrance
of organisms from some source situated elsewhere
in the body, by way of the bloodstream.
Endogenous infections play important role in the
inflammations of uvea.
Types of infectious uveitis. Depending upon the
causative organisms, the infectious uveitis may be
classified as follows:
i. Bacterial infections. These may be granulomatous
e.g., tubercular, leprotic, syphilitic,
brucellosis or pyogenic such as streptococci,
staphylococci, pneumococci and gonococcus.
ii. Viral infections associated with uveitis are herpes
simplex, herpes zoster and cytomegalo inclusion
virus (CMV).
iii. Fungal uveitis is rare and may accompany
systemic aspergillosis, candidiasis and
blastomycosis. It also includes presumed ocular
histoplasmosis syndrome.
iv. Parasitic uveitis is known in toxoplasmosis,
toxocariasis, onchocerciasis and amoebiasis.
v. Rickettsial uveitis may occur in scrub typhus
and epidemic typhus.
2. Allergic (hypersensitivity linked) uveitis. Allergic
uveitis is of the commonest occurrence in clinical
practice. The complex subject of hypersensitivity
linked inflammation of uveal tissue is still not clearly
understood. It may be caused by the following ways:
i. Microbial allergy. In this, primary source of
infection is somewhere else in the body and the
escape of the organisms or their products into the
bloodstream causes sensitisation of the uveal tissue
with formation of antibodies. At a later date a
renewal of infection in the original focus may again
cause dissemination of the organisms or their
products (antigens); which on meeting the sensitised
uveal tissue excite an allergic inflammatory response.
Primary focus of infection can be a minute
tubercular lesion in the lymph nodes or lungs. Once
it used to be the most common cause of uveitis
worldwide, but now it is rare. However, in developing
countries like India tubercular infections still play an
important role. Other sources of primary focus are
streptococcal and other infections in the teeth,
paranasal sinuses, tonsils, prostate, genitals and
urinary tract.
ii. Anaphylactic uveitis. It is said to accompany
the systemic anaphylactic reactions like serum
sickness and angioneurotic oedema.
iii. Atopic uveitis. It occurs due to airborne
allergens and inhalants, e.g., seasonal iritis due to
pollens. A similar reaction to such materials as
danders of cats, chicken feather, house dust, egg
albumin and beef proteins has also been noted.
iv. Autoimmune uveitis. It is found in association
with autoimmune disorders such as Still’s disease,
rheumatoid arthritis, Wegener’s granulomatosis,
systemic lupus erythematosus, Reiter’s disease and
so on.
In phacoanaphytic endophthalmitis, lens proteins
play role of autoantigens. Similarly, sympathetic
ophthalmitis has been attributed to be an
autoimmune reaction to uveal pigments, by some
workers.
v. HLA-associated uveitis: Human leucocytic
antigens (HLA) is the old name for the
histocompatibility antigens. There are about 70 such
antigens in human beings, on the basis of which an
individual can be assigned to different HLA
phenotypes. Recently, lot of stress is being laid on
the role of HLA in uveitis, since a number of
diseases associated with uveitis occur much more
frequently in persons with certain specific HLAphenotype.
A few examples of HLA-associated
diseases with uveitis are as follows:
  HLA-B27. Acute anterior uveitis associated with
ankylosing spondylitis and also in Reiter’s
syndrome.
  HLA-B5: Uveitis in Behcet’s disease.
  HLA-DR4 and DW15: Vogt Koyanagi Harada’s
disease.
3. Toxic uveitis. Toxins responsible for uveitis
can be endotoxins, endocular toxins or exogenous
toxins.
i. Endotoxins, produced inside the body play a
major role. These may be autotoxins or microbial
toxins (produced by organisms involving the body
tissues). Toxic uveitis seen in patients with acute
pneumococcal or gonococcal conjunctivitis and in
patients with fungal corneal ulcer is thought to be
due to microbial toxins.
ii. Endocular toxins are produced from the ocular
tissues. Uveitis seen in patients with blind eyes,
long-standing retinal detachment and intraocular
haemorrhages is said to be due to endocular toxins.
Other examples are uveitis associated with intraocular
tumours and phacotoxic uveitis.
iii. Exogenous toxins causing uveitis are irritant
chemical substances of inorganic, animal or
vegetative origin. Certain drugs producing uveitis
(such as miotics and cytotoxic drugs) are other
examples of exogenous toxins.
4. Traumatic uveitis. It is often seen in accidental or
operative injuries to the uveal tissue. Different
mechanisms which may produce uveitis following
trauma include:
140 Comprehensive OPHTHALMOLOGY
  Direct mechanical effects of trauma.
  Irritative effects of blood products after
intraocular haemorrhage (haemophthalmitis).
  Microbial invasion.
  Chemical effects of retained intraocular foreign
bodies; and
  Sympathetic ophthalmia in the other eye.
5. Uveitis associated with non-infective
systemic diseases. Certain systemic diseases
frequently complicated by uveitis include:
sarocoidosis, collagen related diseases (polyarteritis
nodosa (PAN), disseminated lupus erythematosus
(DLE), rheumatic and rheumatoid arthritis), metabolic
diseases (diabetes mellitus and gout), disease of the
central nervous system (e.g., disseminated sclerosis)
and diseases of skin (psoriasis, lichen planus,
erythema nodosum, pemphigus and so on).
6. Idiopathic uveitis. It may be specific or nonspecific.
i. Idiopathic specific uveitis entities include the
conditions which have certain special characteristics
of their own e.g., pars planitis, sympathetic
ophthalmitis and Fuchs’ hetero-chromic iridocyclitis.
ii. Nonspecific idiopathic uveitis entities include
the condition which do not belong to any of the
known etiological groups. About more than 25
percent cases of uveitis fall in this group.