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1. Peripheral ulcerative keratitis
(PUK)
February 2019 GC.

2. Outline
Introduction
Anatomy
Pathophysiology
Presentation
Etiology and DDx
Management

3. Def.
• A group of Destructive inflammatory diseases
involving the Peripheral cornea whose common Final
pathway characterized by a of sloughing of corneal
epithelium and keratolysis (corneal melting)

4. Def. cont
 It begins with crescentic destructive inflammation at
corneal periphery.
 Is associated with epithelial defects, stromal
inflammatory cells, Progressive stromal melting ,
degradation, necrosis and perforation
 May be associated with Episcleritis, Necrotizing
Scleritis, Iridocyclitis

5. Key features
 Peripheral corneal ulceration
 Unilateral or bilateral
 Progresses circumferentially, posteriorly and may
perforate
 May be association with systemic collagen vascular
diseases.
 Can be a presenting feature of a previously
undiagnosed systemic collagen vascular disorder.
 Frequently requires systemic immunosuppressive
therapy

6. Anatomy
 No clear-cut borders delineating peripheral cornea
 Portion located b/w central 50% of cornea and limbus.
 An arbitrary central limit beginning at 3.5–4.5 mm
from the visual axis extending to junction of ill-defined
transition b/w limbus and conjunctiva.
 Directly adjacent to limbus and internal angle
structures
 Highly vascular zone with associated lymphatic tissue,
scleral collagen, corneal collagen and limbal stem
cells.

7. Why the peripheral cornea?
 Thickest region of the cornea (up to 0.7 mm) with
tight collagen bundle packing
 A vascular arcade originating from the anterior ciliary
arteries extends approx. 0.5 mm into the clear cornea
 Unlike central avascular cornea , peripheral cornea
derives part of its blood supply from Ant conjunctiva
and deep episcleral vessels which are

8. Why…
• unique immunologic characteristics like
Prevalence of Langerhans’ cells,
relatively higher concentrations of IgM,
and higher concentrations of the first
component of complement (C1)

9. Why…
• The adjacent conjunctival blood vessels and
lymphatics provide the peripheral cornea
 Access to afferent and efferent arc of the immune
system
• Source of inflammatory effector cells and cytokines
involved in the production of collagenase and
proteoglycanase, which contribute to corneal
degradation.

10. PATHOGENESIS
• Exact pathophysiologic mechanisms - unclear.
PROPOSED MECHANISMS IN
IMMUNOLOGICAL PATHOGENESIS
 Circulating immune complex deposition
 Autoimmune reactions to corneal antigens
 Hypersensitivity reactions to exogenous antigens
 Evidence suggests that both humoral and cell-
mediated mechanisms (T cell and B cell) are involved

12. Ocular Presentation
 Presenting symptoms of PUK -not specific.
 Foreign body sensation, watering, pain, and
photophobia – epithelial erosion and ulceration.
 Pain is severe - associated scleritis
 Pain without scleral involvement- Mooren’s Ulcer

13.  Decreased Vision - inflammatory process proceeds
centrally or induced astigmatism.
 Photophobia with reduced visual acuity - Associated
anterior uveitis or/and induced astigmatism

14. Slit lamp Examination
 Crescent shaped destructive lesion at juxta limbal
corneal stroma W/in 2mm of limbus ,accompanied by
varying degrees of vaso-occlusion of adjacent limbal
networks
 Epithelial defect
 Stromal thinning w/ yellow white infiltrates –
inflammatory cells
 In early ds., patchy epithelial involvement;stroma –
near normal thickness
 Thinning due to keratolysis (corneal melting), may
occur at any clock hour of the peripheral cornea, with
or w/out an intervening clear zone from limbus

17.  Disease process may progress circumferentially,
centrally, and posteriorly
 Corneal melting may progress very rapidly
 Amount of stromal loss underappreciated due to
debris and necrotic material deposited at the base of
the ulcer.
 Becomes more apparent after scrapings

18. • Frequently limbal, conjunctival, and episcleral
injection occurs.
• Concurrent scleritis denotes a higher likelihood of
active vasculitis
• When PUK is ass w/ scleritis there exists worse
ocular and systemic outcome than when there is
scleritis alone

19. Complications include
Severe Astigmatism,
Secondary bacterial infection ,
perforation,
cataract ,
Glaucoma
Cataract and glaucoma may occur as a result of the
inflammatory process or the use of corticosteroids

20. SYSTEMIC ASSOCIATIONS
• 50% of patients with PUK may have an associated
systemic disease with the large majority being the
collagen vascular diseases (CVDs).
• Rheumatoid arthritis (RA) is most common CVD ass
w/ PUK, likely due to its high prevalence in the
population (affecting 2.5–3% of adults).
• Wegener’s granulomatosis and other ANCA-
associated vasculitides although relatively rare, are an
important cause of PUK.

21. • In up to 25% patients, PUK may be the initial
presenting feature of a potentially lethal
undiagnosed systemic vasculitis.

22. DIAGNOSTIC WORK-UP
 A thorough ocular history, contact lens wear, current
and previous medication for any diseases, trauma, or
surgery
 A comprehensive Systemic review to r/o systemic
diseases ass w/ PUK
 A complete ophthalmic examination to exclude local
pathologies is critical

23. • Tests to exclude infectious etiologies
Corneal scrapings and subject to
1. Gram Stain , KOH
2. Culture
3. Limulus Lysate Assay
• Rapid and reliable method
• Detect minute amounts of Gram Negative endotoxin
• Prompt selection of appropriate anti microbial

24. • LABORATORY INVESTIGATIONS
1. CBC , ESR
2. RF( +ve in 80 % patients with RA)
3. Angiotensin Converting Enzyme ( Sarcoidosis)
4. Anti Nuclear Antibody(ANA) (SLE ,RA)
5. Antibody to Double Strand DNA (anti –ds DNA)(SLE)
6. Antibody to small nuclear ribonucleoprotein (anti-RNP )(SLE)
7. Anti neutrophil cytoplasmic antibodies (ANCA ) c-ANCA in WG
8. Anti CCP
9. Urine Analysis
10. HBsAg
11. FTA –ABS
12. CXR
13. Biopsy of the bulbar conjunctiva adjacent to the ulcerating cornea
should be considered, especially in suspected autoimmune associated PUK.

26. Management
• Medical management
• Surgical Management

27. Medical treatment
Infectious causes need to be excluded by the
appropriate culture techniques
• If infections are suspected- Antimicrobial
therapy administered
• Prophylactic topical antibiotics - prevent
secondary infections

28. 1. ENHANCED LUBRICATION
 Dilutes effect of inflammatory cytokines in preocular
tear film. Many rheumatoid patients have KCS as a
manifest of 2◦ Sjogren syndrome.
 Melting stops or slows down if epithelium made to
heal by Lubricants,Pathching, Bandage Contact
lens

29. 2.Topical corticosteroids
 considered as initial therapy in milder, unilateral
cases (typically when not associated with a systemic
CVD)
 Useful in mild cases of RA-associated PUK
 May be harmful in a subset of vasculitic PUK
because they inhibit new collagen production

30.  Not effective in WG, microscopic polyangiitis,
Churg–Strauss syndrome, and PAN
 In these cases, corticosteroids may promote
progression and even enhance perforation and thus
must be used judiciously.

31. 3. Systemic corticosteroids
 Oral prednisone 1 mg/kg/day- very commonly used
for the a/c
management of more severe cases of PUK.
 If there is progression, pulsed methylprednisolone
(0.5-1.0 g) for 3 consecutive days may be effective.
 Corticosteroids alone may be inadequate to control
the progressive ocular disease process
 Prolonged use of corticosteroids - significant
systemic side-effects necessitating alternative steroid-
sparing immunosuppressive agents

32. 4. immunosuppressive agents
• Have demonstrated some clinical efficacy for
inflammatory eye disease

33. Indications of
immunosuppresivedrugs
 PUK associated with a potentially lethal systemic
disease, such as rheumatoid arthritis, Wegener’s
granulomatosis, relapsing polychondritis, polyarteritis
nodosa
 PUK with associated scleritis
 Bilateral Mooren’s ulcer
 Disease progression despite local conjunctival
resection and tectonic procedures (e.g., tissue
adhesive)

34. IMMUNOMODULATORY/IMMUNO
SUPPRESSIVE THERAPY IN PUK

35. Studies suggest that cyclosporin A with dosages in the
range of 2.5 mg/kg/day may be a reasonable initial
choice for In idiopathic PUK,(especially if
nephrotoxicity is not a concern)

36. 4.Biological agents
 The efficacy of Biologic agents such as the anti-
tissue necrosis factor (TNF) and anti-B cell
monoclonal antibodies in the treatment of RA,
 WG, spondylo-arthropathies, inflammatory bowel
disease as well as other systemic vasculitis suggest
that they have a role.
 • Systemic therapy should be continued for a period
of 6 months to 1 year after initial control of
inflammation has been achieved

38. Surgical Treatment
• Surgical treatments mainly to maintain the integrity
of the globe and are typically palliative.
1.Conjunctival resection
• Temporarily remove the limbal source of local cellular
mediators and collagenases important in progression of
the disease process.
• May be of great diagnostic help

39. 2. Tissue adhesive
 Application of Isobutyl cyanoacrylate glue , forms a
biological barrier b/w host cornea and the
reepithelializing conjunctiva and the immune
components it may carry

40. 3. Patch graft
 When a perforation is too large for tissue adhesive to
seal the leak, some type of patch graft will be
necessary.
 • This may range from a small tapered plug of corneal
tissue to a penetrating keratoplasty

41. 4. Superficial lamellar keratectomy
 arrest the inflammatory process and allow healing
5. Rehabilitative surgical therapy
 Initial lamellar tectonic grafting followed by central
penetrating keratoplasty

42. In advanced cases
LKP is the most widely practiced surgery – in 2 stages
 For an ulcer < 1/2 circle of limbus and the central 7-8
mm of cornea ,uninvolved, crescent shaped lamellar
graft can be used.
 For an ulcer > 2/3 of a circle of limbus where the
central 7-8 mm of cornea is intact, a doughnut
shaped lamellar graft is recommended

43. Conjunctival flaps
 control corneal melting in difficult to manage
microbial keratitis,
 but best avoided in immune mediated disease
 Bringing conjunctival vasculature closer to area of
corneal disease accelerate melting

44. Other
• Amniotic Membrane transplantation-

45. COURSE AND OUTCOME
Depends on
• underlying cause of the PUK and
• on prompt and appropriate management

46.  Many patients with mild or moderate PUK may
maintain good vision if the inflammatory process is
rapidly controlled.
 The prognosis is more guarded when PUK is ass with
a systemic CVD.

47. References
 Yanoff & Duker: Ophthalmology, 3rd ed.
 Duane's Ophthalmology, 2007 Edition
 BCSC 2012 -2013 section8
 Online sources