Infectious Keratitis: Differential Diagnosis & Clinical Considerations

1. Infectious Keratitis:Differential Diagnosis & Clinical Considerations Optometry 8260 Fall 2007 Dr. Jarka

2. Definition of Terms • Make sure you understand the terms- they may be confusing for the new clinician! • Keratitis: Broad term for any inflammation of the cornea; SPK/SPE, infiltrate, and/or ulceration may all be signs; may or may not stain depending on corneal layer involved • Infiltrate: Collection of inflammatory cells and cellular debris; may be epithelial, subepithelial, or stromal; many causes

3. Definition of Terms • Ulcer: Full thickness epithelial break with underlying infiltrate; may or may not be due to active infection (“infectious” vs. “sterile”); a.k.a. “ulcerative keratitis” • Infiltrative keratitis: Term covers many different conditions and etiologies; conditions range in severity from self-limiting to sight-threatening; may progress to ulceration

4. Definition of Terms • Infiltrative keratitis may occur secondary to… • Bacterial etiologies: • Active corneal infection • Non-infectious infiltrate due to exotoxins • Viral etiologies: • Adenoviral infection • Herpetic infection (HSV, HZV) • Fungal infection • Hypersensitivity/toxic inflammatory reactions • Chronic hypoxia

5. Bacterial Ulcerative Keratitis

6. Bacterial Ulcerative Keratitis • Synonyms: Bacterial corneal ulcer, infectious corneal ulcer • Always an urgent, vision threatening condition • Must be ruled out in any case of infiltrative keratitis; if clinical signs are equivocal, treat infiltrate as infectious • EW soft hydrogel CLs are the most common etiology; risk increases significantly in smokers

7. Bacterial Ulcerative Keratitis • Be aware of the potential time-course of infiltrative keratitis. • Some very small lesions caused by virulent organisms can penetrate an intact cornea overnight (Neisseria gonorrhea, Corynebacterium diptheriae, Listeria, Hemophilus) • Be aware that the clinical difference between infectious and noninfectious infiltrative keratitis can be negligible

8. Regional Differences in Keratitis

9. Corneal ulcer/ gram (+) rods

10. Corneal ulcer- Pseudomonas/ gram (-) rods

11. Non-infectious clues Peripheral location Smaller size (-) Fl stain, less edema (-) AC reaction Sectoral injection Little or no pain, photophobia, lacrimation Concurrent lid disease Infectious clues Central location Larger size (+) Fl stain, edema (+) AC reaction 360 degree injection More pain, photophobia, lacrimation EWCLs Bacterial ulcerative keratitis?

12. Bacterial ulcerative keratitis Tx • Important: when in doubt, treat as infectious! • Cultures usually not required, except for atypical presentations (aggressive, large, or central ulcers) • Topical 3rd generation fluoroquinolones have emerged as standard of care, even though not FDA approved for Tx of infectious keratitis • Zymar (gatifloxacin) or Vigamox (moxifloxacin) • 1 gtt. q 15-30 min x 6 hours, then every hour until signs improve, then taper; Ciloxan ung. at bedtime, and if awake overnight? • Some strep, staph & pseudomonas becoming resistant to fluoroquinolones • May add fortified cephazoline, then fortified tobramycin • What about Ciloxan, Ocuflox, Polytrim, Tobrex, etc…? • Must monitor daily until resolution

13. Infection Masqueraders • Many conditions may mimic infectious keratitis • Inflammatory signs and symptoms must be closely evaluated for clues of infection • Primary management aimed at inflammation control; secondary Tx may address underlying cause of inflammation (i.e. staph exotoxins) • Clinician must recognize pathophysiology of keratitis in order to quickly and effectively control patient symptoms and rule out a sight-threatening disorder

14. Contact lens related keratitis • Red eye(s) in a CL wearer should be assumed to be due to CLs until proven otherwise • Signs and symptoms related to inflammation secondary to chronic mechanical trauma, lack of oxygen, and/or solution sensitivity • EW and tight fitting lenses are risk factors • Patient susceptibility quite variable

15. Contact Lens Peripheral Ulcer • Occurs primarily with any hydrogel extended wear contact lenses, though certain patients may present with similar signs and symptoms from daily wear • Inflammatory reaction occurs when cornea has prolonged exposure to S. aureus toxins on the CL, mechanical irritation, and/or hypoxia • Mild to moderate pain/light sensitivity, focal redness

16. CLPU • Focal, peripheral excavation of the epithelium with minimal involvement of Bowman’s layer. • Rare anterior chamber reaction • Minimal lid involvement

17. CLPU

18. CLPU Tx • Primary Tx is discontinuation of CL wear; condition largely self-limiting • May use steroid and/or prophylactic antibiotic until epithelium resolves • Monitor closely if suspicious signs are present or if the patient does not steadily improve

19. Staph-toxic SPK/Marginal keratitis • Represents chronic inflammation of cornea due to Staph toxins in tear film • “4 & 8 syndrome” • Usually concurrent chronic blepharitis and/or meibomianitis, and mild diffuse conjunctivitis. • Variable spectrum and degrees of presentation • Management directed at treating underlying lid / external disease, and reducing corneal and conjunctival inflammation. • While condition is not infectious, antibiosis is wise with use of anti-inflammatory medications.

20. Non-infectious marginal ulcers • Initially treat as infectious (not as aggressively?) • Manage underlying cause (CL compliance, lid disease, etc.) • Steroid often necessary to clear residual infiltrate once underlying cause is controlled • Use caution • Combo medications helpful (e.g. Tobradex)

21. Phlyctenular keratoconjunctivitis • Usually unilateral, with mild gritty or foreign body sensation. • Usually associated with staph signs and symptoms • Phlyctenule (phlycten) = localized, superficial, infiltrative reaction, usually at 4 & 8 o’clock. • Elevated, finger-like projection of fibrous tissue across limbal junction, with overlying pannus • Steroids work well • DDx: Interstitial keratitis, pannus secondary to exposure.

22. Contact Lens Acute Red Eye • Also known as “Tight Lens Syndrome” • Patient wakes due to symptoms or notices symptoms after waking. • No symptoms before sleeping • Usually moderate UNILATERAL pain, redness, photophobia, tearing. • Peripheral and mid-peripheral SEIs with minimal epithelial involvement. • No anterior chamber or lid reaction.

23. CLARE

24. CLARE Tx • No treatment is necessary • Discontinue CL Wear • Antibiotic/steroid combination may be used in severe cases • Antibiotic for microbial prophylaxis • Steroid for inflammation • Clinical Pearl: Use a topical steroid ONLY if certain of inflammatory etiology!

25. Viral Keratoconjunctivitis

26. EKC • Probably most common contagious eye condition encountered by the O.D. • Highly contagious • Possible Preauricular node (PA node) • Traditionally adenovirus 8 (& 4, 11, 13, 19, 37) • Disease progression follows the “Rule of 8’s” • 2-8 days of conjunctivitis (most contagious); moves to fellow eye by end of first week • 2-8 days of SPK • 2-8 days of SEIs • Variable symptoms, intensity, duration

27. Adenoviral Keratoconjunctivitis • Much milder than EKC • Patient usually never presents for care, because symptoms so mild • No PA node • Little to no SPK • Usually no treatment required

28. Subepithelial Infiltrates

29. SEI’s New Old

30. Pharyngeal Conjunctival Fever • Associated with Adenovirus 3 (& 4, 7) • Almost always there is a recent history of sore throat, congestion, and/or cough • Low to moderate fever • Most common in kids 5-15 y.o. • Frequently called “pink eye” by patient & nurses. • May have recent swimming pool exposure (“swimming pool conjunctivitis”) • May be confused with HSV • Like EKC, “may get worse before it gets better”

31. Herpes Simplex Virus (HSV) • MUST rule out HSV with any unilateral red eye • Often misdiagnosed • “One of the great masqueraders” • Leading cause of blindness secondary to corneal disease; leading cause of corneal opacity in children • Decreased corneal sensation greater with recurrent episodes • Cotton wisp test • Recurrent cases: • 75% epithelial • 25% stromal

32. Cotton Wisp Test

33. HSV • HEDS 1 • Topical steroids beneficial in treatment of stromal disease. • No benefit of oral Acyclovir in stromal disease. • Acyclovir not of proven benefit in secondary iritis (but causes no harm) • HEDS 2 • Oral Acyclovir (400 mg b.i.d.) reduces rate of any ocular herpetic outbreak by 41% • Oral Acyclovir reduces rate of stromal herpes by 50% • No proven benefit of adding oral Acyclovir to Viroptic in preventing progression of epithelial disease to stromal.

34. HSV • 20% of “above the waist” HSV caused by Type 2 organism (20% of “below the waist” disease caused by Type 1) • Virulence of outbreaks variable, based on characteristics of individual strains and patient immune response. • Type 2 disease: • 30% increase in prevalence since the 70s • 45 million in U.S. are seropositive • Primary infection worse in women • Growing in the teenage population

35. HSV • Herpes Simplex Virus is almost epidemic in the USA: most common cause of infectious blindness in USA • Almost always UNILATERAL presentation of moderate to severe redness, pain (burning and/or irritation common), photophobia, tearing, and decreased vision • Often a history of cold sores on face • Possible skin lesions • Often patients have multiple episodes

36. HSV • Follicular conjunctival reaction • + PAL • Multiple possible epithelial presentations • Superficial SPK • Stellate Keratitis • Dendritic Keratitis • Geographic Ulcer • Clinician must recognize that stromal involvement and iritis are common clinical variations in presentation! • Lesions show heaped up margins with terminal bulbs that stain with Rose Bengal • + Staining with NaFL • Decreased corneal sensitivity

37. HSV Treatment • Epithelial disease - oral antivirals are of limited usefulness (see HEDS study) • Viroptic 1% Oph Soln q 2 hour up to 9X/day until re-epithelialization; higher doses and increased frequency commonly cause toxic keratitis • Vira-A 3% Oph Ung 5X/day is an alternative therapy or may be used at night for extreme cases • Cycloplegics for comfort (Homatropine 5%)

38. HSV dendrite with rose bengal stain

39. HSV dendrite with NaFlNaFl + rose bengal

40. HSV geographic ulcer

41. Recurrent HSV stromal keratitis with ulcer/previous vascularization

42. HSV stromal keratitis with Wessley ring

43. Herpes zoster (HZV) • Varicella virus (“chickenpox” in kids, “shingles” in adults) • Ocular involvement highly variable, may mimic almost any other anterior segment disease. • Usually severe pain (neuralgia) with lid signs. • Lid signs usually prodrome to eye involvement (Hutchinson’s sign = 75% chance of ocular involvement) • Does not produce true dendrite (infiltrative vs. ulcerative; tapered endings, not end-bulbs) • MUST rule out HSV

44. HZV keratoconjunctivitis with pseudodendrite

45. HZV peripheral ulceration with perforation

46. Other Infectious Keratoconjunctivitis Etiologies

47. Acanthamoeba Keratitis • Protozoan infection • Often SCL history, and exposure to contaminated CL solutions (often homemade) or stagnant water sources • Pain often worse than signs suggest • Often misdiagnosed as stromal HSV • Often diagnosis of exclusion, made after other therapy attempts fail • Cultures & corneal specialist consult is wise • Hospitalization and PK are both almost always eventually required

48. Acanthamoeba Keratitis • Circumcorneal injection and lid chemosis common • A/C reaction present • Does not respond to antimicrobial/antiviral therapy • Two phases • Early phase: Pain and decreased VA not consistent with the corneal appearance. Epithelial and stromal infiltrates present with a possible “radial keratitis”, possible pseudodendrites • Late phase: Stromal ring infiltrate

49. Ring Infiltrate (RedAtlas.org)

50. Acanthamoeba Treatment • Grab bag treatment often requiring hospitalization • Common regimen: • Neosporin Oph Soln 1 gt, q ½ to 2 hours • Propamide isethionate 0.1% (Brolene) 1 gt, q ½ to 2 hours • Itraconazole 400 mg loading dose, 200mg p.o. qd • Polyhexamethyl biguanide 0.02% 1 gt, q 1 hour