3. Viruses DNA DNA n RNA

4. DNA n Alpha (HSV and VZV) n Beta (CMV) n Gamma (EBV)

5. RNA Viruses n Picorna n Papova n Adenoviridae Mumps, Measles, HIV etc Mumps, Measles, HIV etc

6. Properties n Two HSV types- Type I and Type II n Gene analysis of HSV n Strain differences in neuroinvasiveness, neurovirulence, propensity to cause corneal epithelial and stromal disease, responsiveness to steroids etc

9. Epidemiology n Humans - Only natural reservoir n Infection- Direct contact,Salivary droplets n Iatrogenic sources- Hands, Tonometer etc n 60% children infected by 5 years n 80% of neonatal infection by Type II

11. I. Primary infection n Neonatal n Primary

12. Recurrent infection n Blepharitis n Conjunctivitis n Dendritic or Geographic keratitis n Sterile corneal trophic ulceration

13. Recurrent infection n Stromal immune keratitis –Antigen- antibody- complement mediated »IK »Immune rings »Limbal vasculitis »Lymphocyte mediated »Disciform keratitis »Endothelitis

14. Recurrent infection n Trabeculitis n Iridocyclitis

15. Neonatal primary Ocular Herpes n Typically affects perioral region n Systemic manifestation: CNS predominance n Ocular : Conjunctivitis with or without keratitis n Necrotizing chorioretinitis, cataracts, optic neuritis

16. Primary Ocular HSV n Acute first HSV infection of nonimmune host n 3-9 days after exposure to an infected carrier n Virus shedding for 10-14 days and lasts for 2 weeks n Hemmorhagic vesicular periocular dermatitis or blepharitis

17. Primary Ocular HSV n Significant periorbital skin involvement n Skin eruptions localized to the periocular area n Confined to epithelium because of lack of immunologic stimulus

18. Latency n Neuronal cells of trigeminal ganglia n HSV- Neuronal cells and VZV- Support cells n Corneal latency- ?Static or dynamic

20. Pathogenesis of Recurrent disease n Viral strain and host immune responses responsible n Live virus- Dendrite and Geographic ulcers n Sequelae- Sterile trophic ulceration n Stromal reaction- Immune reaction to viral byproducts n ?Actual viral replication

21. HSV Blepharitis n Focal clusters of vesicles along lid margin n Progress to ulceration and heals without scar n Virus shedding for 2 days and lasts for 7 days

22. HSV conjunctivitis n Acute Follicular conjunctivitis n Association of preauricular nodes n Watery discharge with mononuclear infiltrate n Pseudomembranes n Conjunctival dendrites

23. Infectious epithelial keratitis n Caused by live virus n Punctate keratitis, Dendrite, Geographic n Single or multiple, Linear branches, Terminal bulbs and swollen epithelial borders containing live virus n Ulcer extends through the basement membrane

25. Geographic Keratitis n True ulcer- Extends through the basement membrane n Borders flat and subject to change

27. Marginal Ulcer n Patients more sensitive to pain n Ulcer followed by infiltration n No lucid interval and not associated with blepharitis n Epithelial lesion quickly infiltrated with blood vessels

28. Epithelial trophic Keratitis n Neither infectious nor immune n Due to impaired corneal sensation and decreased tear secretion n Irregularity of corneal surface and lack of lusture of Cornea n Results in recurrent epithelial erosions, persistent stromal ulceration and perforation

29. Epithelial trophic keratitis n Trophic ulcers due to residual mechanical damage n Corneal epithelium “ Lies on top” of BM n Diseased epithelium and PMN release collagenases n Oval in shape with smoothborders n Gray thickened borders owing to piling of epithelium

31. HSV stromal keratitis n Hypersensitivity reaction to fixed antigens within the stromal keratocytes or fibroblasts, or endothelium n Active viral infection in the stromal and endothelium secondary to reactivation

32. AAC mediated keratitis n Necrotizing keratitis n Immune rings of Wessley n Limbal vasculitis

33. Necrotizing keratitis n ? Direct viral invasion of stroma n Necrosis, Ulceration, and dense infiltration of stroma with epithelial defect n DD for suppurative keratitis n Far more indolent and has dense vascularization

34. Immune ring n AAC precipitate n Incomplete or complete and is seen in midstroma of central or paracentral cornea n Immune ring can become necrotic

36. Stromal Opacities n Most likely represent AAC immune complexes n Opacities accompanied by haze ( ? Inflammation and oedema)

38. Disciform keratitis n No obvious epithelial defect n Round area of stromal edema n Edema usually spans entire stromal thickness resulting in ground glass appearance n Epithelial bullae can be an accompaniment n KP

39. Stromal neovascularisation n Rapid neovascularisation associated with intense infiltration n Sectoral or complete and may mimic syphilitic IK

40. HSV endothelitis and trabeculitis n Preceded by dendritic ulceration or Increased IOP n Demarcation line of KP between edematous and non edematous areas( ? Localized endothelitis) n HSV antigens have been recovered from AC

42. Infectious epithelial keratitis n Debridement n Topical antivirals for 10-14 days n If persists, check if –Dendritic epitheliopathy instead of keratitis –Neurotrophic keratitis –Resistance. (Vidarabine is useful) –Host immunosuppression

43. Neurotrophic keratopathy n Discontinue all medications, especially antivirals n Boggy rolled epithelium can be mechanically removed to improve reepithelisation n Low dose steroids to counteract low grade inflammation n Therapeutic soft contact lens n Tarsorapphy

44. Immunologic stromal disease n Topical steroids hallmark n Titre dose individually( Customize) n May require treatment for more than 10 weeks n Inadequate treatment most common cause for treatment failure n Flare dose- Never reduce steroids by 50% n “ Drop for Drop”

45. HEDS n Topical Trifluoro thymidine and steroids were better than TF3 and Placebo in reducing the progression of stromal inflammation and in shortening stromal keratitis n No benefit of oral acyclovir for the treatment of stromal keratitis

46. HEDS n Oral Acyclovir given during epithelial keratitis does not prevent stromal keratitis n Reactivation n Previous literature: Recurrence or reactivation of HSV is 25% during 5 years. 80% occurs in the first year n HEDS- 10% stromal keratitis

47. Surgical treatment n Therapeutic contact lenses n Conjunctival flap n Penetrating Keratoplasty

48. PKP for Viral Keratitis n Increased survival rate when rejection treated with concurrent topical steroids and topical antivirals n Prophylactic antivirals are not useful n Reactivation of Virus in the host recipient interface

49. Herpes Zoster keratitis

50. Lids & Conjunctiva n Lid edema, maculopapular rash and a vesicular reaction n Trichiasis, Ectropion, Entropion, Madarosis, Cicatrical contraction n Conjunctival scarring with occasional pseudomembrane formation

51. Cornea n 2/3 of patients n PEK = Coarse SPK,stains with rosebengal n Pseudodendrites n Multiple, elevated lesions,Broader without central ulceration

52. Cornea n Anterior stromal infiltrates n Represent ?stromal reaction to soluble viral antigen n ? Direct viral cytotoxicity n Sclerokeratitis n Keratouveitis

53. Corneal mucous plaques n Occurs several months after HZO n Elevated coarse gray white branching lesions on the surface of swollen epithelial cells n Stain with rosebengal n Variable, migratory and transitory around the cornea n Mechanism- Represent an abnormal epithelial receptor site n Wiping reveals an intact epithelium

55. Disciform keratitis n Weeks or months after the initial episode n Deep central or peripheral disc shaped with intact epithelium

56. Other features Other features n Neurotrophic keratopathy n Exposure keratopathy n Interstitial keratitis n Scleritis and Episcleritis

57. Other features n Uveitis n Ischemic occlusive vasculitis n Segmental iris distortion and atrophy and hemmorhagic hypopyon n Glaucoma n EOM palsies

58. EOM Palsies n 3,4 and 6 can get involved n 31% can demonstrate EOM palsies n Brain stem extension or a localized peripheral nerve vasculitis of orbit n Apical syndrome can develop

59. Features n Acute retinal necrosis n Optic neuritis and retinitis

60. Post herpetic neuralgia n Persists after rashes have abated n Preferential loss of large inhibitory fibres in the nerve with subsequent increase in damaged nociceptive fibres

61. Treatment n Topical Acyclovir has minimal benefit n Immunocompetent person with HZO n Oral acyclovir-800 mg 5 times for a week n IV acyclovir - 30 mg/kg /day if disseminated

62. Topical steroids n Useful in Keratouveitis, Disciform keratitis, sclerokeratitis, episcleritis and trabeculitis) n Predisposes to prolonged treatment n Systemic NSAID required for scleritis, sclerokeratitis etc n Corticosteroids contraindicated in epithelial defects, trophic ulceration

63. Systemic steroids n Large haemmorhagic skin bulla, n Progressive proptosis with ophthalmoplegia n Optic neuritis n Cerebral vasculitis