3. 1. INTRODUCTION
2. CAUSES OF PUK
3. PATHOPHYSIOLOGY OF PUK
4. PATHOPHYSIOLOGY OF MOOREN ULCER
5. CONCLUSION
OUTLINE
4. • Peripheral ulcerative keratitis (PUK) is used to describe a group of
destructive inflammatory diseases involving the peripheral cornea
whose final common pathway is characterized by sloughing of corneal
epithelium and keratolysis (corneal “melting”)
• The vast majority of cases are mediated by local and systemic
immunological processes, although some cases may be infectious in
origin
• PUK may be associated with systemic vasculitides, particularly the
collagen vascular diseases, in about half of the non-infectious cases
INTRODUCTION
5. • The onset of autoimmune PUK generally correlates with exacerbations
of an under lying systemic disease
• In some cases, the ocular finding of peripheral corneal infiltration or
frank stromal melting may be the first sign of the under lying systemic
illness
• Left untreated or inadequately treated, a high number of patients with
autoimmune PUK suffer severe disease-related morbidity and mortality
INTRODUCTION
7. • The unique characteristics and anatomy of the peripheral
cornea contributes to the predilection of this region to be
involved in both local and systemic immunological reactions
• There are no clear-cut borders that delineate the peripheral cornea,
with an arbitrary central limit beginning around 3.5–4.5 mm from the
visual axis and extending out to the junction of the ill-defined
transition between limbus and the sclera and conjunctiva
PATHOPHYSIOLOGY OF PUK
8. • Distinct anatomical differences of the peripheral cornea include
• the greater thickness (up to 0.7 mm) with tight collagen bundle
packing;
• a vascular arcade that originates from the anterior ciliary arteries and
extends approximately 0.5 mm into the clear cornea (providing the
nutritional supply but also access to the efferent arm of the immune
response); and
• accompanying lymphatics, which drain to the regional lymph nodes
(afferent arm of the immune response)
PATHOPHYSIOLOGY OF PUK
9. • The adjacent conjunctival blood vessels and lymphatics not only
provide peripheral corneal access to the afferent and efferent arcs
of the immune system but may be sources of inflammatory
effector cells and cytokines involved in the production of
collagenase and proteoglycanase, which may contribute to
corneal degradation
PATHOPHYSIOLOGY OF PUK
10. • There also are unique immunological characteristics of the
peripheral cornea compared with the central cornea, including the
presence of
1. more Langerhans’ cells,
2. higher concentrations of immunoglobulin M (IgM) and
3. the first component of complement (C1) (important in the
activation of the classic complement pathway), likely caused by
limited central diffusion from the limbal vessels resulting from the
large size of the latter two molecules
PATHOPHYSIOLOGY OF PUK
11. • Although the exact pathophysiological mechanisms of PUK are unclear,
circulating immune complex deposition, autoimmune reactions to
corneal antigens, and hypersensitivity reactions to exogenous
antigens have been proposed, with evidence suggesting that both
humoral and cell-mediated mechanisms (T cell and B cell) are
involved
• Locally produced or circulating immune complexes lodged in limbal
or peripheral corneal blood vessels may activate the classic
complement pathway in the presence of C1 (the recognition unit of the
classic complement pathway)
PATHOPHYSIOLOGY OF PUK
12. • Immune vasculitis resulting in damage to the vessel wall with leakage
and the chemotaxis of various inflammatory cells, proteins, and
proinflammatory cytokines and the production of metalloproteinases by
local resident cells may accelerate and propagate the peripheral
corneal destructive process
• Although autoimmune PUK can be bilateral and extensive, it is usually
unilateral and limited to 1 sector of the peripheral cornea
• The initial lesions appear in a zone within 2mm of the limbus and are
accompanied by varying degrees of vaso-occlusion of the adjacent limbal
vascular network
PATHOPHYSIOLOGY OF PUK
13. • In most cases, the epithelium is absent, and the under lying stroma
thinned in the affected area
• however, if the disease is detected early, epithelial loss may be patchy
and stromal loss kept to a minimum
• Ulceration may or may not be associated with a significant cellular
infiltrate in the corneal stroma, and the adjacent conjunctiva can be
minimally or severely inflamed
• The sclera can also be involved in patients with systemic immune-
mediated diseases (eg, necrotizing scleritis in patients with rheumatoid
arthritis)
PATHOPHYSIOLOGY OF PUK
14. • Although the cause of Mooren ulcer is unknown, precipitating factors
include accidental trauma, ocular surgery, hepatitis C, or exposure
to parasitic infection
• It has been suggested that inflammation associated with a previous injury
or infection may alter the expression of corneal stromal antigens
• These altered antigens stimulate humoral and cell- mediated immune
mechanisms involved in the initiation and perpetuation of corneal
destruction
PATHOPHYSIOLOGY OF MOOREN ULCER
15. • Two clinical types of Mooren ulcer have been described
• Unilateral Mooren ulcer is a slowly progressive disease that typically
occurs in an older patient population and has an equal sex distribution
• The second type of Mooren ulcer, which is more common in Africa,
is usually bilateral, progresses rapidly, and responds poorly to
medical or surgical intervention
• Corneal ulceration frequently progresses to perforation
• Many patients with this form of Mooren ulcer also have coexisting
parasitemia
• It is possible that in this subgroup of West African men, Mooren ulcer
may be
PATHOPHYSIOLOGY OF MOOREN ULCER
16. • It is possible that in this subgroup of West African men, Mooren ulcer
may be triggered by antigen–antibody reaction to helminthic toxins
or antigens deposited in the limbal cornea during the blood-borne
phase of parasitic infection
• Testing for hepatitis C should be considered in patients with Mooren
ulcer–like findings, because there is increased prevalence of comorbid
disease
PATHOPHYSIOLOGY OF MOOREN ULCER
17. CONCLUSION
• PUK is used to describe a group of destructive inflammatory diseases
involving the peripheral cornea whose final common pathway is corneal
melting
• A history of autoimmune and rheumatologic disease is often (but not
invariably) present in affected patients, although in some the ocular finding of
peripheral corneal infiltration or frank stromal melting may be the first sign of
the under lying systemic illness
• PUK occurs most often in association with rheumatoid arthritis, but it is
associated with other conditions as well
• It is important to understand the various pathophysiologic mechanisms in
order to decide on appropriate investigations and treatment options
