NON INFECTIOUS PERIPHERAL ULCERATIVE KERATITIS [PUK]

A Clinical Approach

DR. REKHA GYANCHANDCornea consultant, Lions Eye HospitalBANGALORE

WHAT IS PUK ?

Potentially devastating

Crescent shaped Juxtalimbal corneal stromal

inflammation epithelial defect Stromal infiltrate Progressive stromal melting

If untreated necrosis of entire cornea

WHY IN PERIPHERAL CORNEA ?

Peripheral cornea - Unique anatomical & immunological features

Close to sclera / episclera / conjunctiva Limbal capillary Arcade Avascular central cornea Associated with sub conjunctival

lymphaticsafferent arm IgM in periphery large Langerhans cells Reservoir of inflammatory cells More susceptible to immunological damage

PATHOPHYSIOLOGY OF DAMAGE IN PUKAny inflammatory stimulus in peripheral cornea local cellular & humoral response

complement activation vascular permeability

chemotactic factors for neutrophils (C3a , C5a) neutrophil invasion Inflamm Of Conj proteolytic ,collagenolytic enzymes,leucotrienes

destruction of collagen Collagenase

Corneal thinning

CLINICAL PRESENTATION & DIAGNOSIS

50% Of non infectious PUK due to collagen vascular disease (SLE, RP, PSS, RA,WG, PAN, GCA)

34% of non infectious PUK caused by RA (Tauber et al)

PUK may be initial manifestation of WG & PAN

Moorens ulcer – local autoimmune disease with PUK

CLINICAL PRESENTATION &DIAGNOSIS - II

PUK due to CVD more in females PUK due to Moorens more in males Other causes include

Neoplasia Rosaceae Surgical trauma Blepharitis Inflammatory bowel disease

EXAMINATION IN PUK

Ocular

Systemic

OCULAR EXAMINATION

Symptoms Pain, epiphora, photophobia pain if scleritis (RA, WG, PAN, RP) pain without scleritis ( Mooren’s) Decreased VA

EXAMINATION

Examination of lids Blepharitis Telengiectasis (rosaecae)

Posterior segment examination Posterior scleritis Vasculitis of CVD

SLIT LAMP EXAMINATION-CORNEA

Crescent Juxta limbal Epithelial defect Stromal yellow white

infiltrates Stromal thinning Circumferential /central

spread Adjacent scleral /

conjunctival inflammation

SLIT- LAMP EXAMINATION SCLERA

Associated necrotising scleritis systemic disease

In advanced cases- corneal/scleral melt

SYSTEMIC EXAMINATION Thorough systemic history & examination mandatory Important Questionnaire?

Weight loss, fatigue Skin – facial rashes, ulcers, periungual infarcts(SLE) Respiratory symptoms ( WG, SLE) GI symptoms- pain diarrhoea ( SLE, WG) Musculoskeletal symptoms- joint pain ( RA, SLE) Neurological – seizures, Raynauds (WG, RP, SLE)

Genitourinary- hematuria ( PAN, SLE) Swollen ear lobes (RP, SLE) Deafness (WG) Nasal ulcers/ bleeds ( WG) Saddle nose ( WG, RP)

Differential Diagnosis Of PUK

Other Non Inflammatory Progressive Peripheral Thinning: Terriens marginal degeneration Pellucid marginal degeneration

TERRIENS MARGINAL DEGENERATION

Progressive , non inflam. thinning

No symptoms, V/A Painless Corneal epith intact Begins superiorly No stromal infiltration Lipid deposition Occasional adjacent

conjunctival or scleral inflammation present

Can perforate

Bilateral,painless Inferior corneal crescent

thinning Progressive Clear zone of cornea Epithelium intact Adjacent conjunctiva no

inflammation Corneal ectasia above thinning High against the rule

astigmatism Corneal topography

PELLUCID MARGINAL DEGENERATION

Laboratory Investigations For Non Infectious PUK

CBC ESR CRP URINE ANALYSIS RF ANA (SLE/RA) C ANCA (96% WG) ANTI-ds DNA(SLE) C3/C4 LEVELS CIRCULATING IMMUNE

COMPLEXES

CHEST X-RAY

SINUSES (X-RAY / CT SCAN)

HEPATITIS B,C Ag

LOCAL INVESTIGATIONS

Corneal scraping/culture Conjunctival biopsy

Removes source of collagen Diagnosis of CVD fibrinoid

necrosis,granulomas,vasculitis Diagnosis of Moorens justifies immune

suppression in occult systemic disease

Treatment of Non Infectious PUK

THERAPY

MEDICAL SURGICAL

LOCAL SYSTEMIC

LOCAL THERAPY Goals

Promote epithelial healing– stromal thinning

Control of inflammation Collagenase inhibition– stromal thinning

Promote epithelial healing

• Lubricating drops, gels Avoid epitheliotoxic drugs ( aminoglycosides – tobra, genta;

fluroquinolones—ciprofloxacin) No role of topical antibiotics /

antifungals unless secondary infection

No role of topical steroids/ NSAIDS ( inhibits collagen synthesis—increases melt) Use topical 1% medroxy progesterone (good anti inflammatory, no collagen synthesis

inhibition) Can use topical cyclosporine 0.5- 1% ( local T cell immune modulation) Low dose topical steroids Lid hygeine only in

marginal infiltrates with blepharitis ( staph antigen)

Control of inflammation

Other local medical treatment Blepharitis: lid hygeine Rosaecae: erythromycin ointment;

metronidazole

SYSTEMIC THERAPY

Systemic collagenase inhibitors Tetracycline 250 mg QID Doxycycline 100 mg OD Systemic steroids + cytotoxic

immunosuppressives

INDICATIONS FOR IMMUNE SUPPRESSION

PUK associated with proven CVD like RA, PAN, RP, WG, PSS, GCA, Churg-strauss angitis

If PUK associated with necrotising scleritis

If PUK unresponsive to aggressive conventional medical or surgical therapy

DRUGS USED

High dose oral prednisolone 1- 1.5 mg / kg BW or

Pulsed IV methyl prednisolone ( 0.5- 1g) started first as cytotoxic immunosuppression takes 4 – 6 weeks for action

Drug of choice– oral cyclophosphamide ( 2 mg/ kg / day) adjust to clinical response, adverse effects

DRUGS USED

Methotrexate, azathioprine, cyclosporine-A

Methotrexate : DOC in RA ( 7.5- 12.5 mg / wk)

Azathioprine: 1.3 mg/kg/day Cyclosporine-A:2.5-5mg/kg/day Monitor CBC,LFT,renal function tests Role of immunologist important Good patient education: long term follow

up systemic nature of disease

Surgical treatment

Tissue adhesives ( cyano acrylate glue ) + BSL

Impending perforation / large thinning/ perforation size < 1-2mm

Delays disease process while patient is on immunosuppressives

infiltration of inflammatory cells

Surgical treatment

Conjunctival resection + superficial keratectomy + glue + BCL

Removes source of cytokines / inflammatory cells

Tectonic lamellar / full thickness corneal / scleral graft – Large Perforation w/ Uveal Prolapse

Simultaneous systemic immunosuppression very important or graft will also melt

LONG TERM MANAGEMENT

Local disease healed• No inflammation• Epithelium intact• Vascularised Corneal

pannus

LONG TERM MANAGEMENT

Long term follow up as relapses Prolonged systemic immune suppression till

underlying disease controlled even if EQ Residual astigmatic correction– increases VA Combination of LK +PK for visual

rehabilitation done with full immunosuppression as surgery can trigger relapse

Cataract surgery when systemic disease under control & under systemic steroids

MOORENS ULCER

Distinct clinical entity in PUK

PUK not associated with CVD

? Local auto immune disorder (altered corneal Ag)

? Role of hepatitis C Ag

Distinguishing features

PUK unilateral / bilateral Pain out of proportion No scleritis Typical overhanging

central edge More aggressive and early

conjunctival resection and keratectomy advisable

Glue + BCL – if impending perforation & increased thinning

Systemic steroids and immuno suppressives only if b/l moorens nonresponsive to local

therapy Cyclophosphamide,

methotrexate : DOC If Hep C Ag + :

interferon alpha 2b ( 3 million units tri weekly SC inj – for 6 months

Conclusion..

Non Infectious PUK is a potentially devastating disorder, can be the initial presentation of a serious collagen vascular disorder. Hence proper diagnosis and aggressive therapy could improve local and systemic morbidity.

THANK YOU!