NON INFECTIOUS PERIPHERAL ULCERATIVE KERATITIS [PUK] A Clinical Approach DR. REKHA GYANCHAND Cornea consultant, Lions Eye Hospital BANGALORE

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 lymphatics  afferent arm   IgM in periphery  large   Langerhans cells  Reservoir of inflammatory cells  More susceptible to immunological damage

PATHOPHYSIOLOGY OF DAMAGE IN PUK Any 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 %  ( 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 mg / kg BW or Pulsed IV methyl prednisolone ( g) 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 ( 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.

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