This document provides information on peripheral ulcerative keratitis (PUK), including its causes, pathogenesis, clinical presentation, diagnosis, and treatment. PUK can be caused by infectious, autoimmune, or inflammatory processes that lead to corneal melting and ulceration. It is characterized by sloughing of the corneal epithelium and keratolysis. Diagnostic testing aims to identify any underlying infectious, autoimmune, or inflammatory conditions. Treatment involves topical corticosteroids, conjunctival resection, systemic immunosuppression, and additional surgeries depending on severity and etiology. Mooren's ulcer is a rare type of PUK that is typically unilateral and responsive to local therapies.

1. PERIPHERAL ULCERATIVE KERATITIS
PRESENTED BY
MAJ ANJANI KUMAR
RESIDENT (OPHTHAL)
MODERATOR
COL SANDEEP GUPTA
PROF (OPHTHAL)

2. REFERANCES

3. Introduction -
• 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”).

4. • Majority mediated by local and systemic immunological processes,
although some of infectious etiology need proper evaluation.
• One half of PUK of non infectious etiology are associated with CVD-
RA, GPA, PAN.
• If not properly treated, PUK can progress to perforation resulting in
significant ocular morbidity, and when associated with a systemic
autoimmune condition, may be potentially life-threatening.

5. ANATOMY AND PATHOGENESIS

6. Characteristics of the peripheral cornea
• thickness (up to 0.7 mm) with tight collagen bundle packing;
• vascular arcade originating from anterior ciliary arteries and extends
approximately 0.5 mm into clear cornea (providing the nutritional
supply but also access to the efferent arm of the immune response)
• Presence of more Langerhans’ cells, higher concentrations of
immunoglobulin M8 and first component of complement (C1),
collagenase and proteoglycanase.

7. Pathogenesis
Locally produced or circulating immune complexes lodged in limbal or peripheral corneal blood vessels
Activation of the classic complement pathway in the presence of C1
Immune vasculitis resulting in damage to the vessel wall
Chemotaxis of various inflammatory cells, proteins, and proinflammatory cytokines and the production of
metalloproteinases
Accelerate and propagate the peripheral corneal destructive process.
Trigger factors-
Trauma/infections
Prior corneal surgery

8. Etiologies of PUK
Ocular Noninfectious
• Idiopathic
• Acne rosacea (ocular)
• Mooren’s ulcer
• Traumatic, postoperative (may be a presenting feature of a systemic autoimmune disorder)
• Exposure/neuroparalytic keratopathy
Ocular Infectious
• Bacterial (Staphylococcus, Streptococcus, Gonococcus [rare])
• Viral (herpes simplex and herpes zoster)
• Amebic (Acanthamoeba)
• Fungal

9. Systemic Noninfectious
Collagen Vascular Diseases/Vasculitis
• Rheumatoid arthritis (common)
• Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides
• Granulomatosis with polyangiitis (previously Wegener’s granulomatosis) (relatively common)
• Polyarteritis nodosa (less common)
• Microscopic polyangiitis (MPA) (less common)
• Churg–Strauss syndrome (less common)
• Relapsing polychondritis (uncommon)
• Systemic lupus erythematosus (less common)
• Progressive systemic sclerosis/scleroderma (rare)
• Giant cell arteritis (very rare)

10. Other Systemic Autoimmune
• Cicatricial pemphigoid (especially with trichiasis) (rare)
• Inflammatory bowel disease (very rare)
• Sarcoidosis (very rare)
• Sjögren’s syndrome
• Leukemia/malignancy (very rare)
• Inflammatory bowel disease (usually associated with a nonulcerative peripheral keratitis)
• Giant cell arteritis (rare)

11. Systemic Infectious
• Gonorrhea
• Bacillary dysentery
• Tuberculosis
• Borreliosis (Lyme disease—very rare)
• Varicella zoster
• Helminthiasis

12. OCULAR MANIFESTATIONS
Foreign body sensation, pain, and photophobia -epithelial erosion and ulceration.
Vision affected –if peripheral inflammatory process proceeds centrally or from induced astigmatism.
Anterior uveitis may contribute to photophobia with reduction of visual acuity.
Pain may be severe if associated scleritis occurs.

13. Progressive Circumferential Peripheral Corneal Ulceration.
(A) A 60-year-old female with idiopathic peripheral ulcerative keratitis. Slit-lamp microscopy demonstrates depth
of stromal necrolysis. There is inflammatory infiltrate at both the peripheral and central edges. (B) Fluorescein
staining

14. The specific clinical findings at presentation will depend on the severity and rate of progression of the disease, as
well as the timing between the onset and clinical evaluation.
Corneal melting, once initiated, may progress very rapidly.
The amount of stromal loss apparent after corneal scrapings are performed to evaluate for infectious causes.
Limbal, conjunctival, and episcleral injections occur frequently.
Concurrent scleritis denotes a higher likelihood of active vasculitis.
The finding of PUK with scleritis portends a worse ocular and systemic outcome than when scleritis occurs alone.
Cataract and glaucoma may occur as a result of the inflammatory processor the use of corticosteroids.

15. RA WITH PUK
Nearly 50% of patients with PUK have an associated systemic disease, with the large majority of these being
the collagen vascular diseases (CVDs).
Rheumatoid arthritis (RA) is the most common CVD associated with PUK, likely due to its high prevalence in
the population (affecting 2.5%–3% of adults).
Pathogenesis
immune complex deposition in the limbal vessels
immune-mediated vasculitis
leakage of inflammatory cells and proteins.
activation of complement system and increases cytokine
production, recruiting neutrophils and macrophages that
release collagenases and other proteases that in turn cause
corneal tissue destruction.
Studies have shown that increased cytokines may also
stimulate an increase in matrix metalloproteinase production
by keratocytes themselves

16. Slit lamp photograph of the right eye of a 50-year-old patient
with RA and acute marginal stromal infiltrates
Slit lamp photograph of diffuse anterior and posterior scleritis
in a 67-year-old patient with RA

17. Keratolysis may occur associated with necrotizing scleritis in inflamed or noninflamed eyes.
Loss of stroma occurs in regions of clear cornea and may progress to descemetocele formation.
Corneal and scleral stromal lysis with wound dehiscence has also been described after cataract, strabismus, and other
intraocular surgeries in patients with RA, often in patients with preoperative KCS.
Postoperative scleral or corneal necrosis may, in fact, be the first manifestation of a systemic vasculitic process, and such
patients should receive an appropriate autoimmune work-up with a consulting rheumatologist to rule out RA or other
autoimmune disorders.
Slit lamp photograph of necrotizing scleritis 1 week after
phacoemulsification with intraocular lens implantation. Note
eroded running suture and prolapsed uveal tissue

18. PUK WITH GPA
Non specific disease causing conjunctival and scleral inflammation leading to corneal thinning if systemic therapy
delayed.
PUK may manifest at the onset.
Ocular involvement in 50-60%
Dx- ANCA
Focal necrotizing scleritis with peripheral keratitis (box) in
Wegener's granulomatosis
Peripheral anterior stromal and subepithelial infiltrates (1) in
Wegener's granulomatosis

19. PAN
Ocular findings occur in a minority of patients (10–20%),[ most commonly involving the retinal vessels. This may occur
secondary to the hypertension or there may be vasculitis involving retinal vessels.
Conjunctival nodules caused by edema and necrosis of conjunctival vessels as well as uveitis have also been reported.
Anterior segment findings are infrequent but include scleritis, sclerokeratitis, and peripheral ulcerative keratitis.
The scleritis may be diffuse and associated with peripheral keratitis and ulceration, or more focal with peripheral corneal
Mooren's-like ulceration.
Bilateral peripheral ulceration with perforation in a patient with microscopic polyarteritis has also been reported.
Treatment focuses on the systemic disease and involves the use of corticosteroids and, more importantly, cytotoxic agents,
which have markedly improved the outcome.

20. Peripheral ulcerative keratitis in a patient with polyarteritis
nodosa
Clinical characteristic similar to Mooren’s Ulcer.
Hbs Ag + in 50%
Development of PUK in a pt with already diagnosed
PAN on therapy – indication for vigorous therapy

21. GCA
Giant cell arteritis (GCA) or temporal arteritis is a systemic vasculitis of medium to large vessels.
Ocular manifestations include ischemic optic neuropathy, amaurosis fugax, diplopia and ophthalmoplegia, and retinal vessel
occlusion.
Formed visual hallucinations have also been reported. Anterior segment findings are infrequent. Scleritis has been reported.
Anterior segment ischemia with diffuse corneal edema, hypotony, and keratic precipitates has been reported, presumably
secondary to inflammation involving the long posterior ciliary arteries.
Bilateral peripheral corneal ulceration without infiltration has been reported in a single case of temporal arteritis.
Peripheral ulcerative keratitis in a patient with giant cell
arteritis

22. DIAGNOSTIC AND ANCILLARY TESTING
• Workup of Peripheral Ulcerative Keratitis (Noninfectious)
• CBC
• RF
• Anti-CCP
• c-ANCA and p-ANCA
• ESR and CRP, CIC
• Urine analysis
• Radiographs
• Chest
• Sinus

23. Medical treatment
• Topical Corticosteroid- in milder PUK, not a/w CVDs
• Systemic corticosteroids- oral prednisone 1 mg/kg/day- acute
management of more severe cases of PUK.
• If progression occurs, pulsed methylprednisolone (0.5–1.0 g) for three
consecutive days may be effective

24. Indications for Systemic Immunomodulatory
Therapy in Peripheral Ulcerative Keratitis (PUK)
1. PUK associated with a potentially lethal systemic disease, such as
rheumatoid arthritis, Wegener’s granulomatosis, relapsing
polychondritis, polyarteritis nodosa
2. PUK with associated scleritis
3. Bilateral Mooren’s ulcer
4. Disease progression despite local conjunctival resection and tectonic
procedures (e.g., tissue adhesive)

26. Surgical treatment
• Conjunctival resection
• Tissue adhesives & Flaps/AMT
• Lamellar graft/ PK

27. Mooren’s ulcer
Rare, chronic, painful, peripheral ulcerative keratitis (PUK), was first described in detail as a clinical entity by Mooren
in 1867.
Unilateral, occurs in the fourth decade or later, responsive to local surgical and medical therapy.
The disease is strictly a peripheral ulcerative keratitis (PUK), with no associated scleritis.
Bilateral, more resistant to systemic immunosuppression, painful, relentless, progressive destruction of the cornea, usually in
younger individuals (third decade), many of whom are of African descent
Pathogenesis- autoimmune reaction against a specific target molecule in the corneal stroma, which may occur in genetically
susceptible individuals.
Both cellular and humoral mechanisms have been postulated.
The conjunctival epithelium demonstrates increased levels of several inflammatory mediators.
Mooren’s ulcer in patients with concurrent hepatitis C respond to IFN-α- common antigenic source.

28. Acute Mooren’s Ulcer. Peripheral thinning and an
overlying epithelial defect are present in an inflamed eye.
Mooren’s Ulcer. Peripheral thinning is present in a
relatively quiet eye in this patient who had a history of
Mooren’s ulcer, now in remission

29. An early Mooren's ulcer characterized by a crescent-shaped
peripheral ulcer concentric to limbus; the leading edges are
undermined and infiltrated.
Clinical Features
Symptoms
redness, tearing, and photophobia, but pain is typically the
outstanding feature.
The pain often is incapacitating and may well be out of
proportion to the inflamma
decreased visual acuity, which may be secondary to associated
iritis, central corneal involvement, or irregular astigmatism due
to peripheral corneal thinning.

30. Signs
Typically, Mooren's ulcer begins as a crescent-shaped gray-white infiltrate in the peripheral cornea.
Epithelial breakdown and stromal melting follow this. Eventually it develops into a characteristic chronic crescent-shaped
peripheral ulcer.
The ulcer is concentric to limbus; the leading edges are undermined, infiltrated, and deepithelialized.
The ulcer progresses circumferentially and centrally. As it progresses, it creates an overhanging edge at its central border.
Though the ulcer may begin as a shallow furrow in the peripheral cornea, over time it may involve the limbus. The adjacent
conjunctiva and sclera are usually inflamed and hyperemic.

31. As the disease progresses, the ulcer spreads in three directions: peripherally, centrally, and rarely into sclera.
Behind the advancing edge of the ulcer, healing may take place. This healing is in the form of corneal epithelialization and
vascularization. Associated with this is scarring and thinning.
The healed area remains clouded. In an advanced case of Mooren's ulcer most of the cornea is lost, leaving behind a central
island surrounded by area of grossly thinned, scarred, and vascularized tissue .
Although the disease is characterized by progressive thinning, corneal perforation is uncommon and is more common in
eyes with peripheral as compared to total ulceration.
Iritis sometimes is associated with Mooren's ulcer. Hypopyon is rare unless secondary infection is present. Glaucoma and
cataract may complicate the process

32. Advanced Mooren's ulcer characterized by gross destruction of cornea,
leaving behind a central island of tissue

33. Differential Diagnosis
Although Mooren's ulcer has a characteristic clinical picture, several other diseases can present with peripheral keratitis and
ulceration. The differential diagnosis of Mooren's ulcer includes other inflammatory and noninflammatory causes of
peripheral thinning and ulceration.
ocular systemic
Terrien’s Marginal degenerations Tuberculosis
Pellucud Marginal degenerations Varicella zoaster
Idiopathic furrow degeneration Syphillis
Staphylococcal marginal Keratitis Sarcoidosis
Rosacea keratitis CVDs
Exposure keratitis RA
GPA

34. Diagnosis
As previously stated, Mooren's ulcer is idiopathic, and the characteristic features must occur in the absence of any systemic
process that may cause PUK. Thus, it is a diagnosis of exclusion.
Detailed history with specific attention to history of systemic illness, and a complete ocular and systemic examination.
The laboratory studies should include complete and differential blood cell counts, platelet counts, erythrocyte sedimentation
rate, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, chest X-ray examination, liver enzymes,
and fluorescent treponemal antibody absorption test.
Additional testing is done as indicated by the review of systems and physical examination. Infectious etiologies should be
excluded by appropriate cultures, because microbial keratitis can rapidly progress and is usually amenable to antibiotic therapy.

35. Treatment
The goals of treatment in Mooren's ulcer are to stop the ulcerative process and allow reepithelialization of the cornea.
Four strategies underlie most of these treatments: (1) local immunosuppression, (2) systemic immunosuppression, (3)
removal of local stimulatory antigens, and (4) removal of distant stimulatory antigens.
The following stepwise approach to management is recommended: (1) topical corticosteroids, (2) conjunctival resection, (3)
systemic immunosuppression, and (4) additional surgery.
Topical corticosteroids: These are used aggressively on an hourly basis, along with topical prophylactic antibiotics and
cycloplegic medications. When the cornea shows signs of reepithelialization the steroid therapy is tapered gradually over
months. It is important to monitor for cataracts and an increase in intraocular pressure.
Conjunctival resection: This removes involved conjunctiva and blocks collagenase and the immune response to corneal
antigen by providing a biological barrier. In this procedure, conjunctiva adjacent to the corneal ulcer is resected up to 2 clock
hours on either side to bare sclera and extends 3–4 mm from the limbus. Postoperatively, topical corticosteroids and
antibiotics are continued.

36. Systemic immunosuppression
Those cases of bilateral or progressive Mooren's ulcer that fail therapeutic steroids and conjunctival resection will require
systemic cytotoxic chemotherapy to bring a halt to the progressive corneal destruction. It is better to start this treatment
sooner rather than later, before the corneal destruction has become too extensive for surgery.
Systemic corticosteroids can be given to suppress inflammation and arrest progressive corneal thinning. The recommended
dosage for oral prednisolone is 1–1.5 mg/kg body weight/day. The dosage is adjusted according to the severity of the
disease and is tapered slowly when improvement occurs. Alternatively, to avoid side effects associated with long-term
corticosteroid therapy, patients can be given intravenous pulse therapy of methylprednisolone.
Other systemic immunosuppressants used in the management of Mooren's ulcer are: cyclophosphamide (2 mg/kg/day),
methotrexate (7.5–15 mg once weekly), and azathioprine (2 mg/kg/day). The degree of fall in white blood cell count is
considered as the most reliable indicator of immunosuppression produced by cyclophosphamide.
Oral ciclosporin A (3–4 mg/kg/day) has been successfully used to treat a case of bilateral Mooren's ulcer unresponsive to
local therapy as well as systemic immunosuppression. Ciclosporin A works by suppression of the helper T-cell population
and stimulation of the depressed population of suppressor and cytotoxic T cells present in these patients.
Although immunosuppression is effective, close follow-up is necessary to ensure that the white blood cell count does not
reach a dangerously low level. The administering physician must be vigilant about adverse effects of these cytotoxic and
immunosuppressive medications.

37. Additional Surgery
Keratoepithelioplasty
Lamellar keratectomy
Lamellar keratoplasty- The procedure removes antigenic targets of the cornea, prevents immunological reactions, reconstructs
the anatomy and prevents it from perforating, and improves vision. The surgical procedure involves removal of necrotic
ulcerative cornea and reconstruction of anatomical structure using lamellar donor lenticule. The surgical plan depends on the
shape of the ulcer and infiltration of the cornea. If the ulcer is smaller than a half circle of the limbus and the central cornea is
not involved, a crescent-shaped lamellar graft is used. If the ulcer is larger than two-thirds of a circle of the limbus and the
central cornea is intact, then a doughnut-shaped lamellar graft is used. If the central cornea is involved, a full lamellar graft is
used to maintain visual acuity. For perforation of peripheral cornea, double lamellar grafts comprising a thin inner graft with
endothelium for repair of perforation and another lamellar graft on the surface whose shape depends on the shape of the
ulcer is used. Chen at al. reported a cure rate of 73.7% after the first procedure of LKP plus 1% ciclosporin A eyedrops and a
final cure rate of 95.6%.
Tissue adhesives and bandage contact lens
Tectonic grafts (Patch graft or penetrating keratoplasty)

38. Prognosis
• The clinical course, response to therapy, and eventual prognosis of
Mooren's ulcer are related to disease presentation.
• The disease can present as a unilateral disorder, a bilateral
nonsimultaneous disorder, or a bilateral simultaneous disorder.
• Patients with unilateral disease usually respond best to therapy and
have the best prognosis.
• Patients with simultaneous bilateral disease usually do the worst.
Patients with nonsimultaneous bilateral disease fall in between.

39. Staphylococcal Marginal Keratitis
• Staphylococcal marginal keratitis, also referred to as catarrhal infiltrates or ulcers, is a peripheral
corneal disorder characterized by inflammatory infiltration that may lead to ulceration.
• It is likely the most common disorder of the peripheral cornea.
• Thygeson first reported the frequent association of catarrhal infiltrates with chronic conjunctivitis
due to Staphylococcus.
• These peripheral ulcers differed from central ulcers in their relatively benign course and the lack
of bacteria found in corneal scrapings.
• Accordingly, these lesions are thought to represent an antibody response to toxins rather than
direct bacterial invasion.

40. Pathogenesis
Similar to phlyctenulosis, bacterial antigens from chronic staphylococcal colonization of the eyelids are thought to trigger an
immune response in a sensitized cornea.
The immune response is most likely a type III hypersensitivity reaction resulting in immune complex deposition in the
peripheral cornea.
These complexes activate the complement pathway, attracting neutrophils to the site forming an opacity (catarrhal
infiltrate).
In support of this theory, immunoglobins and C3 complement have been demonstrated in marginal infiltrates.Further, Gram
and Giemsa staining of corneal scrapings show neutrophils but no organisms.

41. Clinical features
Patients with staphylococcal marginal keratitis usually present with pain, photophobia, foreign body sensation, and
conjunctival injection. The symptoms are typically mild to moderate and are not specific.

42. Staphylococcal marginal keratitis. Fluorescein examination reveals overlying epithelial defects. These lesions can be
confused with infectious keratitis, and microbial evaluation may be indicated

43. Differential diagnosis
1) infectious corneal ulcers. Infectious ulcers are usually more painful, more central in location, and have a modest anterior
chamber reaction.
2) Herpes simplex virus keratitis - HSV infection begins with an epithelial defect followed by an infiltrate, which is the reverse
order in staphylococcal marginal keratitis. Dendritic or geographic epithelial lesions and profound corneal hypoesthesia are
other distinguishing features of herpes simplex keratitis.
3) peripheral ulcerative keratitis caused by collagen vascular diseases (e.g. rheumatoid arthritis). staphylococcal marginal
keratitis tends to have a benign course, collagen vascular-associated ulcers tends to be more severe and progressive.
staphylococcal marginal keratitis responds rapidly to topical corticosteroids, whereas patients with peripheral corneal ulcers
related to collagen-vascular disease often need systemic immunosuppression to control inflammation and may worsen on
topical corticosteroids

44. Diagnostic evaluation
• The diagnosis of staphylococcal marginal keratitis is usually made based on
clinical findings.
• In cases where there is an overlying epithelial defect, exclusion of
infectious processes is important.
• corneal scrapings for culture- with an associated epithelial defect and a
significant anterior chamber reaction/equivocal diagnosis
• Microbial evaluation is also recommended if clinical improvement is not
observed or if the infiltrates progress despite therapy.

45. Treatment
• Topical corticosteroids (i.e. fluorometholone, loteprednol, and prednisolone acetate) are the
mainstay in the treatment of acute marginal staphylococcal infiltrates.
• In cases of corneal stromal infiltrates without epithelial breakdown, topical corticosteroids may
be used immediately. In cases with epithelial breakdown and stromal ulceration, a broad-
spectrum topical antibiotic should be used briefly prior to starting topical corticosteroids.
• Eyelid hygiene is used to remove bacteria from the lashes and lid margins, while antibiotic
ointments are used to limit bacterial colonization.
• Systemic antibiotics (i.e. tetracycline, doxycycline, erythromycin) may be indicated when the
disease is recurrent or if there is significant meibomian gland disease.
• Recently, a topical form of azithromycin has become commercially available that is applied to the
eyelid and may provide broad-spectrum antibioisis with once-daily dosing.