ETIOLOGY, PATHOLOGY AND PATHOGENESIS OF CORNEAL ULCER

ETIOLOGY, PATHOLOGY AND PATHOGENESIS OF CORNEAL ULCER

1. ETIOLOGY, PATHOGENESIS & PATHOLOGY OF CORNEAL ULCER By Dr . SAMARTH MISHRA

2. . WHAT IS CORNEAL ULCER??? Corneal ulcer may be defined as discontinuation in normal epithelial surface of cornea a/w necrosis of the surrounding corneal tissue. Pathologically it is charecterised by oedema & cellular infiltration.

3. TOPOGRAPHICAL ( MORPHOLOGICAL ) CLASSIFICATION: CORNEAL ULCER ( ULCERATIVE KERATITIS): DEPENDING ON LOCATION : a) central corneal ulcer b ) peripheral corneal ulcer DEPENDING ON PURULENCE a) purulent corneal ulcer or suppurative corneal ulcer (most bacterial & fungal Corneal ulcer ) b) non-purulent corneal ulcers( viral, chlamydial & allergic Corneal ulcer) DEPENDING UPON ASSOCIATION WITH HYPOPYON: a simple Corneal ulcer (without hypopyon) b) hypopyon corneal ulcer

4. . DEPENDING UPON DEPTH OF ULCER: a) superficial Corneal ulcer b) deep Corneal ulcer c)corneal ulcer with impending perforation d) perforated corneal ulcer DEPENDING UPON SLOUGH FORMATION : a) non-sloughing corneal ulcer b) sloughing corneal ulcer

5. BACTERIAL CORNEAL ULCER: (causative organisms) Staphylococcus aureus Pseudomonas pyocyanea Streptococcus pneumoniae E.coli Proteus Klebsiella N.gonorrhoea N.meningitidis (can invade intact corneal epithelium) C.diphtheriae

6. Pathogenesis and pathology of corneal ulcer: 4 stages: infiltration,active ulceration,regression,cicatrization. STAGE OF INFILTRATION STAGE OF ACTIVE ULCERATION STAGE OF REGRESSION STAGE OF CICATRIZATION

7. . Damaged epithelium invasion by offending agents Terminal course depends on virulence of agent,host defence mechanism and treatment received. Course of ulcer maybe: a)become localized and heal b)penetrate deep l/t perforation. c)spread fast as sloughing corneal ulcer. A]PATHOLOGY OF LOC ALIZED CORNEAL ULCER: 1. Stage of infiltration: PMN/lymphocytes into epithelium from peripheral circulation. Necrosis may occur.

8. . 2.Stage of active ulceration: results from sloughing of epithelium and bowmen’s memb. & necrosis Ulcer wall project s(swelling of lamellae by imbibition of fluid & packing by leucocytes). ulcer floor shows grey infiltration & sloughing. Hyperemia of circumcorneal vessels. purulent exudates. vascular congestion of iris ‘& ciliary body. Iritis d/t absorption of toxins from ulcer. Exudation into anterior chamber from vessels of iris & cilary body may lead to formation of HYPOPYON ( sterile,fluid ) Ulcer progress laterally diffuse superficial ulceration . Ulcer progress deep  descemetocele/perforation.

9. . 3.Stage of regression: host defense mechanism (humoral /cellular & appropriate t/t ) Line of demarcation devp.( leucocytes  neutralize & phagocytose the offending org. ,debris) Ulcer begins to heal & epithelium starts growing over the edges. 4.stage of cicatrization: Healing continues. Fibrous tissue laid down( corneal fibroblasts & endothelial cells) Stroma thickens & pushes the epithelial surface anteriorly. inolves epithelium only  no scarring bowman’s memb . scar forms ( nebula) Macula & leucoma results after >1/3 rd of corneal stroma.

10. . B] PATHOLOGY OF PERFORATED CORNEAL ULCER: ulceration deepens  reaches descemet’s memb.  descemetocele. straining,coughing etc l/t perforation. After perforationaquaous leaks,IOP falls,iris-lens diaphragm moves forward. Small perforation,opposite to irispluggs & cicatrization proceeds. Commonest end resultadherent leucoma. C] PATHOLOGY OF SLOUGHING CORNEAL ULCER: d/t highly virulent agent/low resistance. Whole cornea sloughs,iris becomes inflammed exudates block pupil. Exudates organize to form PSEUDOCORNEA . This pseudocornea is weak & thin, so bulges forward along with plastered iris tissue ectatic cicatrix ANTERIOR STAPHYLOMA.

11. Perforated corneal ulcer

12. SPECIFIC BACTERIAL CORNEAL ULCERS( charecteristics ): STAPH AUREUS:  rapidly progressive. moderate ant. Chamber reactn with endothelial plaques/hypopyon. round, oval,yellowish-white with dense infiltration & distinct border. stromal microabscess with an ill defined border may develop. NON-AUREUS STAPH. : cause oppertunistic infectn.  >85% of eyelid cultures from normal population are +ve for non- aureus staph. m/c isolated org. from bacterial keratitis . severe ulcers with dense infiltration may occur if untreated

13. . STREP. PNEUMONIAE/ PNEUMOCOCCUS: after corneal trauma,dacryocystitis etc  acute,purulent,rapidly progressive with a deep stromal abscess. ant. Chamber reactn is severe with marked hypopyon.  ”hypopyon corneal ulcer” by pneumococcus.  ”corneal ulcer with hypopyon” hypopyon d/t any other cause. charecteristic feature of hypopyon corneal ulcer caused by pneumococcus is called “ULCER SERPENS”. NOCARDIA ASTEROIDES: gram +ve,acid fast bacillus with branching filaments. produces indolent ulcers after minor trauma particularly in exposure to contaminated soil. nocardia can survive in neutrophils & macrophages a/w production of superoxide dismutase.

14. . Pseudomonas: m/c gram –ve org isolated from severe keratitis. a/w soft contact lens . rapid progression,dense sromal infiltration. marked suppuration,liquefactive necrosis & descemetocele formation or corneal perforation are charecteristic. Neisseria: invade intact epithelium. l/t rapid perforation. B.cereus: chr . By distinct stromal ring infiltrate remote from the site of injury. rapid progression to stromal abscess. corneal perforation.

15. FUNGAL/MYCOTIC CORNEAL ULCER: Incidence has increased d/t injudicious use of antibiotics & steroids. Antibiotics: Disturb the symbiosis b/w bacteria & fungi. Steroids: make fungi facultative pathogens(actually symbiotic saprophytes). ETIOLOGY: Filamentous fungi: Aspergillus( m/c ), Fusarium, Alternaria, Cephalosporium, Curvularia, Penicillium YEASTS: Candida albicans, Cryptococcus MODE OF INFECTION: A) Injury by vegetative material. E.g: leaf,thorn,crop etc. ( field workers affected ) B)Injury by animal tail

16. . C) Secondary fungal ulcers: immunocompromised pts. CHARECTERISTIC FEATURES: a)dry looking,greyish white,rolled out margin b)feathery finger like extension (in stroma underlying intact epithelium). c)sterile immune ring( of wesseley ) i.e a yellow line of demarcation seen d/t fungal Ag- host Ab reaction. d) multiple,small, sattellite lesion seen. e) non-sterile ,thick ,immobile,big hypopyon seen d/t fungal hyphae invasion in contrast to bacterial hypopyon( sterile, mobile). f)symptoms milder than the clinical signs.

17. fungal ulcer with deep stromal infiltration and sattellite lesions.

18. close up view of stromal infiltrations

19. Stromal infiltrations and sattellite lesions.

20. VIRAL CORNEAL ULCER affect conjunctiva & cornea,so typical lesion  keratoconjunctivitis . Etiological agents: HSV,HZV,Adenovirus etc CLASSIFICATION OF HSV KERATITIS : 1)Infectious epithelial keratitis: a) cornea vesicles b) dendritic ulcer c) geographical ulcer d) marginal ulcer 2 ) neurotrophic keratopathy/ trophic ulcer/ metaherpetic ulcer/indolent ulcer 3) stromal keratitis: a)necrotizing stromal keratitis b)immune stromal keratitis

21. . 4) endothelitis: a) disciform b)diffuse c)linear The m/c recognized clinical manifestation of infectious epithelial keratitis are dendritic & geographic ulcer. small vesicles in epithelium (punctate epithelial keratopathy) vesicles coalesce dendritic ulcer geographic ulcer

22. . In immunocompromised  arrested @ the vesicle stage. vesicles may coalesce to form a raised dendritic lesion (displaces fluorescin(-ve stain)) This raised lesion, which is clinically the precursor of dendritic ulcer in immunocompetent host, may not progress to a dendritic ulcer in the immunocompromised host & therefore may not be recognized as infectious epithelial keratitis. So, all pts with HSV corneal vesicles should be recognized as having infectious keratitis & treated promptly. Hsv  two types. Hsv 1 (above waist), hsv 2 (below waist) Hsv are epitheliotrophic,but may become neurotrophic.

23. DENDRITIC ULCER: dendron =tree( greek ) Typical lesion of recurrent epithelial keratitis. Irregular,branching,linear lesions with terminal bulbs & swollen epithelial borders which contain live virus. TRUE ULCER , as it extends through basement membrane. Stains +ve for fluorescin along the length of lesion

24. . swollen borders  actually raised (stain –ve with fluorescin). Rose bengal stain which stains devitalised cells ,is typically taken up by swollen epithelial cells at ulcer border. After ulcer heals  abnormal appearing epithelium (for several weeks) HSV DENDRITIC EPITHELIOPATHY ( dendritic in shape but not ulcerated, represents ulcer healing epithelium) D/D : a) varicella zoster pseudodendrites b) recently healed epithelial defects Diff. from HSV because,these are raised rather than ulcerated & do not stain fluorescin.

25. Geographic ulcer: When dendritic ulcer is no longer linear. A widened dendritic ulcer. TRUE ULCER Has swollen border that contains live virus. The scalloped or geographic borders are imp. to recognise to diff this lesion from healing abrasions & neurotrophic keratopathy, which tend to have smooth border.

26. . EPIDEMIOLOGIC STUDY : wlhemus et al : geographical ulcer  22% of all cases of infectious epithelial keratitis.  a/w with use of topical steroids. Liesegang : geographical ulcer  4% of inf ep keratis cases.  not a/w topical steroids use.

27. Marginal ulcer: Another manifestation of hsv inf epi. keratitis. Proximity to limbus  a/w unique features. Infiltrated quickly by WBCs from nearby blood vessels. Typical presentation: anterior stromal infiltrate underlying the ulcer & adjacent limbal injection. Patient more symptomatic d/t intense inflammation. D/D : staphylococcal marginal(catarrhal) disease.

28. . HSV marginal ulcer staph. Marginal infiltrate Etiology:  active HSV  immunologic response to staph Ag Epithelial always absent(if present,late) defect Neovascn often never Progression centrally circumferentially Blepharitis unrelated usually Location any meridian typically @2,4,8,10 “o’’clock position

29. Sequelae: 4 recognized sequelae: Complete resolution. dentritic epitheliopathy stromal scarring, “ghost figures” or “footprints” of HSV. subsequent stromal inflammation (in 25%)

30. Neurotrophic keratopathy / trophic ulcer: who have had infec.epi.keratitis  at risk. Arises from impaired corneal innervation in combination with decreased tear secretion. Oval,smooth border ( in contrast to geograph. ulcer) Stroma at ulcer bed develops typically a grayish white opacification. Complications: stromal scarring,neovascularisation,necrosis,perforation,secondary bacterial infection. Irregularity of corneal surface  lack of normal corneal lusture punctate epithelial erosion persistent epithelial defect stromal ulceration.

31. HERPES ZOSTER OPHTHALMICUS:  d/t reactivation of latent virus. A)MICRODENDRITIC EPITHELIAL ULCER: peripheral & stellate rather than dendritic in shape. in contrast to HSV dendritis,these have tapered ends which lacks bulbs. B)NEUROPARALYTIC ULCER: occur as a sequelae of acute infection & gasserion ganglion destruction.

32. Mooren’s ulcer:( chr . Serpiginous ulcer/rodent ulcer/’ ulcus rodens’ ) Ulcus rodens: term by Mc kenzie:1854 Idiopathic corneal ulcer. Severe,inflammatory,painful,peripheral ulcerative keratitis. Diagnosis of exclusion ETIOLOGY: A) idiopathic degenerative condition. B) ischaemic necrosis resulting from vasculitis of limbal vessels. C) d/t enzyme collagenase & proteoglyconase produced from conjunctiva. D) autoimmune d/s: Ab against corneal epithelium present in serum. E) a/w HCV,helminthiasis ( molecular mimicry to cross reacting epitopes of cornea, Ag-Ab reactn to helminth @ peripheral cornea provokes inflammation & ulceration)

33. . Clinical varieties of mooren’s ulcer: A)BENIGN FORM: - unilateral -slow progress -elderly -mild to mod. Symptoms -respond well to t/t B) VIRULENT FORM: -bilateral -rapidly progressive -younger pt -scleral inolvement(high) -a/w pain -doesnot respond to t/t

34. . FEATURES: starts @ corneal margin as gray infiltrates. coalesce to form shallow furrow over whole cornea. peripheral  central progression ulcer undermines epithelium & superficial stromal lamellae & forms whitish overlying edge base--> becomes vascularised RARELY perforates,sclera uninvolved. D/D: Terrien’s marginal degeneration.(non inflammatory,thinning of cornea’epithelium intact) Pellucid marginal degeneration Senile furrow degeneration. Staph. Marginal keratitis.

35. Non-infectious ulcers: Tiny tears: may also cause ulcers. Can form from direct trauma,scratches,or particles such as sand,glass,metal. Such injury make it easier for bacteria to invade & cause a serious ulcer. DRY EYES :( SICCA) e.g sjogren’s syndrome CHEMICAL BURNS: alkali /acidic burn THERMAL /RADIATION BURNS D/T EXPOSURE KERATITIS: lagophthalmos,lid abnormalities,facial palsy,proptosis,thyroid d/s. ATOPIC: d/t follicles / pappila VITAMIN –A DEFICIENCY : dietary deprivation,secondary d/s that affect fat absorption & storage like celiac d/s and cystic fibrosis. BASEMENT MEMBRANE ABNORMALITIES: microcysts,evidence of map-dot-finger or anterior stromal dystrophies IMMUNE RELATED D/S: wegener’s granulomatosis,RA,other collagen vascular d/s.

36. Thank you