Bacterial corneal ulcer

common corneal infection

1. Bacterial corneal ulcer Dr. K. Vasantha M.S., F.R.C.S., Edin Director RIO Chennai (Rtd)

2. Bacterial keratitis implies any form of corneal inflammation either superficial, interstitial or deep caused by bacteriae When this inflammation is accompanied by a loss of epithelium, it is termed a Corneal Ulcer. Bacterial ulcer

3. Gram positive bacteriae : Staphylococcus aureus, epidermidis and others Streptococcus pneumoniae. Viridans, pyogenes Corynebacterium Enterococcus Bacillus species Propionibacterium acnes Micrococcus spp, Peptostreptococci, Clostridium perfringens Etiology

4. Pseudomonas aeruginosa Neisseria species Haemophilus species Moraxella species Serratia marcescens Proteus sp., Acinetobacter sp., Enterobacter sp, E. coli, Klebsiella sp., Eikenella sp. Pasteurella multocida, Xanthomonas sp., Gram negative bacteriae

5. Aerobic, nonfermenting gram negative rods Achromobacter xylosoxidans and Stenotrophomonas maltophilia are important causes for contact lens induced keratitis. These are resistant to fluoroquinolones and aminoglycosides Actinomycetes including Nocardia are common in developing countries With orthokeratology lenses Pseudomonas, S.aureus, Acanthamoeba and Stenotrophomonas are found Other organisms

6. Normally the epithelium protects the cornea from getting infected. But these bacteriae can penetrate the epithelium Neisseria gonorrhoeae, Neisseria meningitidis Corynebacterium diphtheriae Haemophilus aegypticus Listeria species Bacteriae that can penetrate the corneal epithelium

7. Ulcers can occur as secondary infection from the conjunctival commensals, from the lids or from the sac when it is inflamed. This will happen when there is an abrasion. This is the reason why when there is a chronic dacryocystitis it must be immediately dealt with Diabetes and immuno suppressives will also predispose the person to infection Contact lens wear Predisposing factors

8. Trichiasis – predisposing factor

9. Watering, pain and redness usually following injury. Defective vision. More if the ulcer is in the center Lid edema, muco purulent discharge Circum corneal congestion, sometimes conjunctival congestion also. Chemosis if there is severe inflammation Opacity in the cornea which will take up fluorescein stain as the epithelium will be abraded. Signs and symptoms

10. Pupil will be constricted and sluggishly reactive due to irritation to the iris. This toxic reaction can produce hypopyon which will be sterile in bacterial ulcer. In fungal ulcer fungal hyphae may be present. Injury with vegetative matter should make one suspect fungal etiology If chronic dacryocystitis is present Pneumococcal infection must be thought of Signs

11. Stage of progressive infiltration Stage of active ulceration Stage of regression Stage of cicatrization Stages

12. Characteristics Staphylococcus aureus Suppuration is the hallmark Yellow – white, oval, densely opaque ulcer with relatively clear surrounding cornea with or without hypopyon Two types of stromal infiltration: - small, discrete, peripheral anterior stromal infiltrates (free of replicating bacteria) - large, severe, central stromal infiltrates (replicating bacteria present) Tissue damage irreversible and leads to permanent scarring

13. Staphylococcal ulcer

14. Often seen when chronic dacryocystitis is present Suppuration and cicatrization are seen together. Ulcer progresses on one side when the other side is healing. Hypopyon will be present as this causes severe iridocyclitis See the sutures made for sac excision Pneumococcal ulcer

15. See the vascularization at 3 o clock and ulcer advancing towards 9 o clock

16. Pseudomonas ulcer

17. Irregular ulcer with thick greenish mucopurulent exudate and ground glass appearance of surrounding cornea (mushy/soupy stroma) Presence of hypopyon Rapid course – liquefactive necrosis, Descemetocoele and perforation in 1 or 2 days Most common pathogen in bacterial keratitis associated with contact lens wear Pseudomonas ulcer

18. This is a commensal organism present on the skin and conjunctiva Opportunistic infection Usually causes secondary infection on HSV keratitis, or on bullous keratopathy Here the ulcer is on a leucoma Staphylococcus epidermidis

19. Usually uniocular, mild, paracentral or perilimbal Central grey infiltrate – ulcer with grey membranous base Second area of infiltration around it in the deep layers of stroma with clear area in between Infiltrated margin lacking and remaining cornea relatively clear Moraxella

20. Moraxella ulcer - don’t miss the small hypopyon

21. Commonest cause is Streptococcus viridans Other etiologic agents: like Staph. epidermidis, Pseudomonas, Mycobacteria, Enterococci , Strep. pneumoniae , Peptostreptococcus and Haemophilus also can rarely cause crystalline keratopathy Serratia marcescens also will give raise to satellite lesions Crystalline keratopathy

22. Corynebacterium also can cause ulcer in preexisting corneal lesions Bacillus species will cause a rapidly progressing ulcer. There will be a ring infiltrate remote from the site of injury Enterobacteriaceae will give raise to a shallow ulcer with grayish white pleomorphic suppuration opaque stroma and ring infiltrates -> -> Other organisms

23. When you see an ulcer the following tests must done to find the causative organism Smear KOH suspension Culture Detection of antigens, antibodies and endotoxins Immunoglobulins PCR Confocal microscopy – not possible to see bacteriae as they are only 0.5 microns in size Investigations

24. Apply topical anesthetic and wait for 3 – 5 mins for the anesthetic to drain off Remove the purulent material with a cotton swab and discord Use a Kimura’s spatula or a surgical blade to take the sample. This is preferably done under a slit lamp. The spatula can be sterilized with flame or 70% alcohol. Contamination by eye lashes is avoided by using a speculum Immediate transfer needed due to small sample Collecting and processing the samples

25. Gram stain: for bacteria, yeasts, cysts of Acanthamoeba. Can detect 60 – 70% of bacteriae. Fungal hyphae are Gram negative or faintly stained walls with unstained protoplasm Giemsa: viral and Chlamydia inclusion bodies, polymorphs and mononuclear cells besides the above microbes Ziehl-Neilson: Mycobacteria and Nocardia Acridine orange: bacteria, fungi and Acanthamoeba cysts Stains used

26. Differential staining

27. Blood agar: for aerobic bacteriae and fungi esp. Fusarium Chocolate agar: Haemophilus, Neissaria and Moraxella Sabouraud’s dextrose agar: fungus Thioglycollate broth: both aerobic and anaerobic Non nutrient agar with E. coli – Acanthamoeba Thayer Martin agar: to isolate Neisseria Brain heart infusion: filamentous fungi and Yeast Lowenstein Jenson for Mycobacteria Culture

28. Not satisfactory because of Small sample Prior antibiotic use Many organisms are difficult to grow – Streptococci and Propionibacterium Polymicrobial keratitis can occur. It is difficult to differentiate this from contamination So while specificity is satisfactory sensitivity is poor Smear and culture

29. Elisa for detecting different antigens Serological tests for IgG and IgM to detect viruses and Microsporidia Limuluslysate test: to detect endotoxins Eubacterial PCR is done for all bacteriae Investigations

30. A DNA sequence determination is coupled with bioinformatic analysis to detect matches between the sample and a data base of reference genome sequence. Rapid and highly accurate identification is possible Next generation sequencing

31. Aim of the treatment To reduce the number of organisms as much and as quickly as possible To reduce the detrimental changes to the cornea caused by the inflammation Treatment

32. Atropine eye drops are given to cause dilatation and cycloplegia. This will reduce pain as ciliary spasm which is the cause for the pain is relieved Dilatation will break any synechiae and also prevent further synechiae from forming Atropine reduces the tear secretion and there by increases the lysozomal content of the tears It also separates the corneal lamellae and helps in penetration of the drops applied Treatment

33. Pupil dilated with atropine

34. If chronic dacryocystitis is present sac excision has to be done As diabetes may predispose to infection and delay healing, this must be checked for History must be taken regarding use of immunodepressants and immunosuppression Treatment

35. Broad spectrum fortified antibiotic drops like Gentamycin and Tobramycin for gram negative organisms Cefuroxime 500 mg in 2 ml if mixed with 8 ml of tear substitute will give a fortified i.e. 50 mg in one ml solution Loading dose for the first half an hour or so and then every hour initially Once healing starts it can be tapered a little but not like steroids as tapering might cause resistance Treatment of bacterial ulcer

36. Has a broad spectrum – even against penicillin and methicillin resistant bacteriae Acts against anaerobes and atypical mycobacteriae Has a higher solubility than the earlier antibiotics Minimum concentration needed is low It is bactericidal Toxicity and allergenicity are low Advantages of fluoroquinolones

37. Moxifloxacin is less active against Pseudomonas but more active against Mycoplasma than Gatifloxacin. It is less likely to give raise to resistance as two mutations are needed. Moxifloxacin is self preserved and hence preservatives are not needed Since it reaches a higher concentration in the anterior chamber development of mutation are prevented Gatifloxacin acts against even Chlamydia and Mycoplasma Fluoroquinolones

38. Recommended drugs Alternative drugs No organism Cefuroxime + Tobramycin or Ciprofloxacin Bacitracin Gentamicin Ofloxacin Gram positive cocci Cefuroxime Bacitracin Vancomycin + Tobramycin Gram negative cocci Cefuroxime Ciprofloxacin Fortified Ceftriaxone Gram negative bacilli Tobramycin or Ciprofloxacin Gentamicin Ofloxacin Gram negative diplobacilli ( Moraxella sp. ) Cefuroxime or Ciprofloxacin Fortified Ceftriaxone Ofloxacin Topical antibiotic therapy based on Gram stain findings

39. Antibiotic Concentration available Diluent (ml) Final concentration Shelf life Amikacin 1gm/4ml 16 50mg/ml 30 days Ampicillin 250mg 5 50mg/ml 4hrs Bacitracin 50,000 U 5 10,000 U/ml 7days Carbenicillin 1gm 10 100mg/ml 3days Antibiotics

40. Antibiotic Available conc Diluent (ml) Final conc Shelf life Cefuroxime 500mg 8 50mg/ml 4days Gentamycin 80mg/2ml 2 20mg/ml 30days Penicillin G-K 10million units 10 1 lakh U/ml 4days Polymyxin B 5 lakh units 10 50,000 U/ml 3days Tobramycin 80mg/2ml 2ml 20mg/ml 30 days

41. Antibiotic Available concentration Diluent (ml) Final concentration Shelf life Vancomycin 500mg 10 50mg/ml 4days Methicillin , Moxalactam 1gm 20 50mg/ml 4days Cefamandole 500mg 10 50mg/ml 4days Chlorhexidine 0.2% w/v (2mg/ml) 5.6ml 0.3mg/ml

42. How to assess healing Active healing

43. Symptoms will be less Congestion will be less The ulcer will stop progressing The edges will become rounded Hypopyon will disappear The cornea around the ulcer will become clearer as the edema comes down How to assess healing

44. Compliance must be checked Change the antibiotics if it is different as per the culture report It must be remembered that with the small sample we get with ulcers the results may not be accurate Resistance to even fluoroquinolones are developing Decision regarding therapeutic keratoplasty must be taken before the ulcer reaches the peripheral cornea If ulcer is not healing

45. Even when an ulcer heals a scar is produced which will cause defective vision A small peripheral scar may not affect vision . If the scar is central mechanical obstruction to vision is caused. A nebular opacity or a peripheral opacity especially one with iris adherence can cause astigmatism and affect vision Complications of corneal ulcer

46. Leucoma

47. Opacity - macula

48. Nebular opacity, vascularization and a small ulcer remaining

49. Leucoma with festooned pupil

50. An ulcer may perforate as the stroma dissolves due to infection and by the action of neutrophils If the perforation is in the periphery the iris plugs the leak and the ulcer may heal with an adherent leucoma If the perforation is in the center a fistula will form. When this ulcer heals an anterior polar cataract may form Sometimes if a small ulcer perforates it may help in healing as it acts like a paracentesis Complications

51. Before the ulcer perforates the Descemet’s membrane will with stand for some time as it is elastic. This will cause the membrane to bulge forward giving raise to Descemetocoele At this stage and for small perforations glue with either bandage or bandage contact lens can be used to seal the perforation Glue has a mild antibiotic activity It also blocks the neutrophils which causes further necrosis Perforation

52. Perforated ulcer

53. If the ulcer progresses further it will become a total ulcer. A therapeutic keratoplasty must be done if the ulcer is progressing fast. A rim of normal cornea will give a better result. So TKP should be done before the ulcer progresses to involve the peripheral cornea Since the eye is inflamed the chances for getting a clear graft is poor. There is a danger of the infection occurring in the graft also Since large grafts will be needed rejection and glaucoma are more common Complications

54. If the infection involves all the layers of the eye it is called panophthalmitis. Once this happens the eye may have to be eviscerated. If the infection is controlled at this stage the eye will become phthisical. Panophthalmitis

55. RE PKP done for leucoma LE eviscerated