Interstitial keratitis

interstitial keratits

1. INTERSTITIAL KERATITIS Dr. Ankush Deepak Weginwar

2. Definition Interstitial keratitis (IK) is a non-suppurative inflammation characterized by cellular infiltration and vascularization of the corneal stroma with minimal primary involvement of the corneal epithelium or endothelium

3. T he disorder has a multitude of causes The disease process can be caused by direct invasion of microorganisms or by an immune response against exogenous or endogenous antigens within the corneal stroma . Congenital syphilis is classically associated with IK. IK is a clinical manifestation of both infectious and noninfectious diseases

4. Causative Organisms Bacterial infection Parasitic infection Syphilis Leishmaniasis Tuberculosis Onchocerciasis Leprosy Trypanosomiasis Lyme disease Acanthamoeba keratitis Brucellosis Microsporidiosis Trachoma  

5. Causative Organisms Viral infection Systemic disease Herpes simplex virus Cogan's syndrome Herpes zoster virus Sarcoidosis Epstein-Barr virus Lymphoma Mumps   Rubeola   HTLV-1  

6. Syphylitic Stromal Keratitis Jonathan Hutchinson (1828–1913 ) recognized his first case of keratitis associated with congenital syphilis in 1849 and collated his articles dating from 1858 into a monograph in 1863 Hutchinson described syphilitic keratitis ‘as a diffuse haziness near the centre of the cornea of one eye’ that became ‘densely opaque by the spreading and confluence of these interstitial opacities’ Stromal keratitis due to syphilis was formerly called interstitial keratitis or parenchymatous keratitis ( keratitis parenchymatosa ) Luetic keratitis (from lues venerea) is an occasional epithet

7. Early stage of syphilitic keratitis . Acute stromal keratitis with ‘cherry-red’ limbal congestion

8. D rawing of stromal keratitis caused by congenital syphilis , showing central corneal inflammation with edema and peripheral corneal neovascularization

9. Stage Onset Laterality Prevalence Early congenital syphilis Birth Usually bilateral Rare Late congenital syphilis 5–20 years of age Usually bilateral Occasional Early acquired syphilis 6 weeks to 6 months after primary chancre Usually unilateral Rare Late acquired syphilis 1–20 years after primary chancre Usually unilateral Uncommon Syphilis and the Cornea

10. Stromal Keratitis in Congenital Syphilis Onset Stromal keratitis is the most common, and sometimes the only, sign of late congenital syphilis Rare before age 2 K eratitis typically begins between 5 and 15 years of age and hardly ever after age 30. Nearly twice as many girls are affected as boys, but among young adults this gender imbalance disappears. Onset in females clusters between 7 and 13 years of age,suggesting a possible hormonal influence

11. Stromal keratitis usually begins as an inflammatory infiltration that has a slight preference for the superior cornea and deeper stroma A faint stromal haze and swollen endothelial cells may appear before symptoms are noticeable . Without corticosteroid therapy, corneal inflammation may remain mild and localized, but often blooms into diffuse stromal keratouveitis and inflammatory edema resembling a ground-glass cornea Acute stromal keratitis with active corneal neovascularization Corneal Inflammation

12. Left Acute stromal inflammatory edema with neovascularization. Middle Corneal inflammation with dense superficial and deep neovascularization. Right Partial clearing with regression of vascularization. Progression of syphilitic stromal keratitis

13. Syphilitic corneal corruption takes myriad forms. The epithelium stays intact but can temporarily erode over superficial opacities Nascent punctate infiltrates clump together or align parallel to the limbus before coalescing Multiple stromal infiltrates may arise at varying levels in the cornea Curvilinear inflammation in the deep stroma is an odd phenomenon called keratitis linearis migrans or keratitis parenchymatosa annularis that starts with one or more spindly infiltrates that lengthen, extend posteriorly, and then advance

14. Microcystic epithelial edema is common, and bullae may form The stroma can thicken to 600 µm or more Wrinkling of the deep stroma and Descemet's membrane creates stellate, striate, circinate, or crisscross folds Frosty corneal edema with blunted sensation can resemble disciform endotheliitis

15. Corneal Neovascularisation New blood and lymphatic vessels often – but not always – invade the cornea during syphilitic keratitis Superficial capillaries bud from venules of the limbal arcades Deeper vessels arise as terminal branches of the anterior ciliary vessels Vascular tufts insinuate between stromal lamellae to head for the inflamed zone Stromal vessels may conform to a fascicular pattern in one sector, or invade radially from various directions

16. Corneal neovascularization associated with syphilitic stromal keratitis. The left drawing shows various forms of superficial stromal vessels that form terminal loops and arborescent or brush forms. The right-hand figure depicts radiating vessels of the deep stroma

17. The extent of neovascularization depends on the severity of inflammation and the use of antiinflammatory drugs Without corticosteroid treatment, a neovascular fretwork forms over several weeks Ultimately a florid stage is reached at the peak of the inflammatory reaction Once the cornea is vascularized, the inflammatory process subsides

18. Uveitis Anterior uveitis Iridocyclitis commonly attends stromal keratitis and iritis can precede the onset of syphilitic keratitis Posterior uveitis Intermediate uveitis, posterior uveitis or retinal vasculitis seldom occur during active stromal keratitis Bilateral keratitis Unilateral stromal keratitis due to late congenital syphilis is not a typical pattern . In 80% of patients with stromal keratitis caused by congenital syphilis the contralateral cornea becomes inflamed.Bilateral involvement may happen simultaneously

19. Other systemic features in Congenital Syphilis E arly congenital syphilis occurs in children between 0 and 2 years old After, they can develop late congenital syphilis Symptomatic newborns, if not stillborn, are born Premature with hepatosplenomegaly S keletal abnormalities P neumonia B ullous skin disease known as pemphigus syphiliticus

20. blunted upper incisor teeth known as Hutchinson's teeth inflammation of the cornea known as interstitial keratitis deafness from auditory nerve disease frontal bossing (prominence of the brow ridge) saddle nose (collapse of the bony part of nose) hard palate defect swollen knees saber shins short maxillae protruding mandible A frequently-found group of symptoms is Hutchinson's triad, Hutchinson's teeth (notched incisors), K eratitis D eafness occurs in 63% of cases Treatment (with penicillin) before the development of late symptoms is essential

21. Stromal Keratitis in Acquired Syphilis Onset Keratitis is very uncommon in acquired syphilis Exceptional during early mucocutaneous syphilis and secondary syphilis Stromal keratitis is typically a feature of late syphilis Onset generally starts 2–15 years after acquiring syphilis , but has rarely been delayed more than 20 years

22. Many patients do not recall a primary chancre or previous symptoms of secondary syphilis and usually have few other signs Keratitis may be more likely if syphilis was acquired at a young age Corneal trauma can be a precipitating factor Syphilitic stromal keratitis has not occurred during HIV/AIDS

23. Corneal inflammation Stromal keratitis associated with acquired syphilis resembles that of congenital syphilis but is usually unilateral and less severe. Stromal inflammation begins with lymphocytes infiltrating the peripheral or central cornea, with a modest predilection for the superior cornea A limpid haze may resolve and be subclinical, but can evolve to deep stromal keratitis Corneal inflammation evokes stromal blood vessels but neovascularization is scarcer and scantier in acquired syphilis than in congenital syphilis Mild iridocyclitis may be present but is seldom intense

24. Stromal keratouveitis manifested by extensive stromal edema and deep neovascularization in acquired syphilis.

25. Keratitis usually remains localized rather than becoming diffuse Necrotizing inflammation of the posterior cornea may effloresce centrally or peripherally and simulate an abscess Recrudescent stromal keratitis can follow abrupt discontinuation of topical corticosteroid therapy Recurrent stromal keratitis uveitis, and scleritis can occur months to years later Systemic antisyphilitic treatment does not prevent bilateral keratitis or recurrent ocular inflammation

26. Inflammatory stromal edema of the superior cornea .. Recurrent stromal keratitis of the deep central cornea 5 months later

27. Other Systemic Signs of Secondary acquired syphilis E nlarged lymph nodes M aculopapular rash over the trunk, palms, and soles (mucous patches are infectious) P ainless erosions of the mouth and rarely the conjunctiva Sudden hearing loss and A cute arthritis Long-lasting stigmata of prior secondary syphilis may be subtle, H ypo- or Hyperpigmented spots on the skin P atchy alopecia of scalp hair, eyebrows, or eyelashes People with late acquired syphilis who develop stromal keratitis are usually otherwise asymptomatic but can later have cardiovascular complications, gummas, and neurosyphilis

28. Management Laboratory Investigation (Serologic tests) Treponemal tests Nontreponemal tests Fluorescent treponemal antibody absorption (FTA-ABS) Venereal Disease Research Laboratory (VDRL) test T. pallidum immobilization (TPI, Nelson-Mayer test) Rapid plasma reagin (RPR) test    Hemagglutination treponemal test for syphilis (HATTS) Automated reagin test (ART)    Microhemagglutination assay for T. pallidum (MHA-TP)    T. pallidum hemagglutination assay (TPHA) particle agglutination (TP-PA) latex agglutination (TPLA)    Enzyme immunoassay (EIA) for treponemal antibodies   

29. Treatment Status Treatment Infant with early congenital syphilis Aqueous penicillin G 50 000 units/kg intravenously every 8–12 hours for 10–14 days Child (<12 years old) with late congenital syphilis Aqueous penicillin G 50 000 units/kg intravenously every 8–12 hours for 10–14 days Adolescent (>12 years old) or adult with late congenital or acquired syphilis but without neurosyphilis Benzathine penicillin G 2.4 million units (or 50 000 units/kg) intramuscularly once weekly for 3 consecutive weeks Adolescent or adult with neurosyphilis Aqueous penicillin G 3–4 million units intravenously every 4 hours for 10–14 days

30. Antiinflammatory therapy Topical corticosteroids Surgical Penetrating keratoplasty is the preferred surgical procedure for treating residual corneal opacification caused by syphilis A triple procedure of corneal transplantation, cataract extraction, and intraocular lens implantation is an option for syphilitic keratopathy with cataract

31. Prevention level General clinical use High-risk individual Primary prevention Provide prenatal screening and prevention practices for sexually transmitted diseases Treat expectant mothers with syphilis and provide accessible treatment for people with early syphilis Secondary prevention Correctly diagnose ocular syphilis by selective serologic testing Prevent visual loss by early recognition and appropriate treatment of stromal keratitis Tertiary prevention Use adequate therapy to reduce sight-threatening complications Correct permanent visual disability by keratoplasty Prevention strategies for syphilitic keratitis

32. Non Syphilitic keratitis Cogan’s Syndrome Typical Cogan's syndrome is strictly defined as nonsyphilitic, noninfectious IK associated with vestibuloauditory disease manifested by a sudden, usually bilateral onset of tinnitus, sensorineural hearing loss, vertigo, nausea, and vomiting similar to Menière's disease However , it is unlikely that Cogan's syndrome represents a single disease

33. Cases of atypical Cogan's syndrome, where ocular inflammatory disease other than IK is associated with vestibuloauditory disease, have been described In addition, Cogan's syndrome has been associated with a number of underlying systemic vasculitides such as polyarteritis nodosa,Wegener's granulomatosis,and rheumatoid arthritis Cogan's syndrome, in its classic description, probably represents the clinical manifestations of an immune response against antigens present in both the corneal stroma and inner ear. This disease process can involve ocular structures in addition to the cornea, such as the choroid (atypical Cogan's syndrome), or cause a systemic vasculitic disease such as polyarteritis nodosa

34. Clinical manifestations Approximately half of patients with Cogan's syndrome present with typical and/or atypical ocular symptoms, O ne-third with vestibuloauditory symptoms, and the remainder with both Patients may also describe a history of fever, headache, bloody diarrhea, anthralgia, myalgia, or preceding upper respiratory infection . A nonsyphilitic IK is the predominant ocular feature of typical Cogan's syndrome, often accompanied by iritis or subconjunctival hemorrhage The IK can be unilateral or bilateral and is often associated with decreased vision, severe eye pain or irritation, lacrimation, and photophobia

35. Slit lamp photograph of the cornea in a patient with a long history of Cogan's syndrome extensive corneal inflammation extensive neovascularization cellular infiltration of the stroma.

36. Slit lamp photograph of the cornea with broad oblique illumination shows interstitial keratitis in a patient with Cogan's syndrome. Stromal scarring ( 1 ) G host vessels ( 2 )

37. Factors differentiate Congenital S yphilis from Cogan's syndrome IK in congenital syphilis Insidious onset L imbal distribution, C orneal scarring Positive serologic tests and other systemic signs The IK of Cogan's syndrome Sudden onst Patchy distribution, R arely causes progressive scarring ( probably because of earlier diagnosis and treatment) Although both diseases lead to hearing loss, vestibulatory system dysfunction with vertigo, nausea, and vomiting are rarely found in congenital syphilis

38. Diagnosis Leukocytosis Eosinophilia E levated ESR P ositive association of human leukocyte antigen HLA B17 Treatment Low-dose topical steroids for IK High-dose systemic corticosteroids for inner ear disease Prednisolone acetate 1% one drop per affected eye may be administered hourly to q.i.d.

39. Nonsyphilitic Bacterial Infection Mycobacterial infection IK is a well-recognized ocular manifestation of systemic acid-fast mycobacterial infection by tuberculosis or leprosy Mycobacterium tuberculosis enters the body primarily via inhalation Macrophages deliver the bacilli to the lymphatic system, where they gain access to the bloodstream Hematogenous spread to the eye can result in uveitis, particularly choroiditis; retinal vasculitis; conjunctivitis; scleritis; and keratitis

40. Corneal photograph of a patient with interstitial keratitis associated with tuberculosis. Note characteristic sectoral, peripheral corneal involvement with stromal vascularization

41. Tuberculous IK is generally unilateral Inflammation may involve either the anterior or posterior stroma Cellular infiltration is often peripheral or quadrantic and is followed by localized edema, and later stromal vascularization may occur with or without development of significant scarring or corneal thinning The natural course lasts weeks to months

42. Treatment Topical corticosteroids can hasten the resolution of active disease , supporting the theory that the IK results from a localized immune response to tuberculin antigens Associated uveitis may be treated with topical cycloplegic agents Treatment for the underlying tuberculosis is required

43. Mycobacterium Leprae In contrast to tuberculous IK , corneal involvement in leprosy is B/L, presence of bacilli throughout the stroma supports an infectious rather than an immunologic etiology The superior cornea is often involved primarily with deep infiltration of lymphocytes, macrophages M . leprae organisms accompanied by stromal edema, which may progress to involve the central cornea Vascularization may occur as a late sequela of disease, and corneal opacification is permanent, should it occur The comorbidity of corneal nerve involvement may contribute to the poorer prognosis of these cases

44. Treatment World Health Organization advocates a multidrug therapeutic regimen of daily dapsone and clofazimine and monthly rifampin and clofazimine for multibacillary disease. Topical corticosteroids for IK and cycloplegics for uveitis can be employed with careful monitoring of the corneal epithelium for neurotrophic and neuroparalytic disease as well as toxic reactions

45. Lyme disease Lyme disease is caused by infection with the spirochete Borrelia burgdorferi via the Ixodes scapularis deer tick

46. Signs of disease have been separated into three stages Stage 1 (Early localisied infection) Flulike illness and the pathognomonic skin lesion Bull’s eye lesion, erythema migrans and follicular conjunctivitis Stage 2 (Early disseminated infection) Facial palsy,meningitis,neck stiffness and photophobia Stage 3 (Late disseminated infection) Ocular inflammatory signs occur in this stage of the disease and include Episcleritis K eratitis U veitis V asculitis E xudative retinal detachment E ndophthalmitis

47. Although keratitis is not a common feature of Lyme disease, the inflammatory pattern is interstitial Involvement is usually bilateral, although it may present in one eye This IK is characterized by multiple poorly defined or nebular stromal opacities These infiltrates have indistinct borders, can be present throughout the corneal stroma, and do not profoundly affect visual acuity Unlike other forms of IK, stromal edema is not a common feature Late vascularization and keratic precipitates with uveitis have been reported

48. Treatment Topical corticosteroids Most reported cases of keratitis were empirically treated with topical corticosteroids while one in three untreated patients developed edema, vascularization, and corneal haze. Late administration of corticosteroid drops remained effective Administration of topical corticosteroids appears to prevent the progression of inflammation to vascularization and scarring S ystemic antibiotic Ceftriaxone (Drug of choice) Azithromycin D oxycycline T etracycline

49. Parasitic Infection Acanthamoeba keratitis A history of contact lens wear and the use of homemade saline solutions Infection with this free-living amoeba is especially difficult to eradicate because the trophozoite form can encyst and elude the immune system and pharmacologic agents. Although a superficial epitheliopathy is an early feature, stromal involvement ensues with infiltration accompanied by edema , which is easily mistaken for herpetic stromal disease.

50. At this stage of interstitial inflammation the diagnostic possibilities are myriad and, if the patient does not have a history of contact lens wear or fresh water exposure the diagnosis may not be obvious Careful examination of the corneal epithelium for a band of intra- and intercellular edema and instability with poor adhesion to the underlying basement membrane should give the clinician adequate indication for diagnostic scrapings and culture using specific media to rule out Acanthamoeba infection

51. Symptoms S evere pain (out of proportion to the degree of inflammation ) Watering P hotophobia B lepharospasm B lurred vision Signs Initial lesions in the form of limbitis , coarse, opaque streaks, fine epithelial and subepithelial opacities, and radial kerato-neuritis , in the form of infiltrates along corneal nerves Advanced cases show a central or paracentral ring-shaped lesion with stromal infiltrates and an overlying epithelial defect, ultimately presenting as ring abscess Hypopyon may also be present

52. Diagnosis Lab Investigations Potassium hydroxide(KOH) Calcofluor white stain Lactophenol cotton blue (for cysts ) Culture on non-nutrient agar Treatment 0.1 percent propamidine isethionate (Brolene) drops Neomycin drops Polyhexamethylene biguanide (0.01%–0.02% solution ) C hlorhexidine Others paromomycin , imidazoles such as fluconazole, itraconazole and miconazole PK in non responsive cases

53. Disease Synonym Agent (vector) Endemic areas Pertinent history Characteristic corneal findings Acanthamoeba keratitis None Acanthamoeba Worldwide Contact lens wear/abuse, freshwater exposure Pain out of proportion to findings. Radial keratoneuritis, early superficial epitheliopathy, stromal infiltration and edema without early stromal neovascularization, late ring infiltrate Onchocerciasis River blindness Onchocerca volvulus (black fly) West and Central Africa, Latin America, Yemen Travel to endemic areas Live microfilariae, peripheral stromal edema, centripetal full-thickness stromal vascularization, complete opacification, absence of thinning Features of Parasitic I nterstitial K eratitis (IK) by etiology

54. Disease Synonym Agent (vector) Endemic areas Pertinent history Characteristic corneal findings Leishmaniasis Baghdad boils, sandfly disease Leishmania spp. (sandfly) Asia, Africa, Latin America, Mediterranean Travel to endemic areas Focal or diffuse IK with deep neovascularization, late thinning, histologic findings of organisms and granulomatous inflammation African trypanosomiasis African sleeping sickness Trypanosoma brucei (tsetse fly) Africa Travel to endemic areas Diffuse neovascularization, severe scarring and thinning, potential perforation Microsporidiosis None Microsporidia Worldwide Immunocompromised status Anterior to midstromal infiltration

55. Viral Infection Herpes Simplex Virus (HSV) Herpes simplex virus is a principal cause of corneal blindness manifest as IK nummular keratitis ulcerative necrotizing stromal keratitis IK hallmarks of Edema N ew vessel formation C ellular infiltration may be present to varying degrees and may be accompanied by scleritis and uveitis, which further complicate this serious condition

56. Pattern of stromal infiltration may be C entral or P eripheral F ocal or M ultifocal S uperficial or Full thickness Wessely-type immune ring, if present, support the diagnosis Treatment Tab Acyclovir 400 mg BD Topical corticosteroids

57. Varicella-zoster virus (VZV) Herpes zoster is another common cause of IK One of the many ocular manifestations of zoster is stromal infiltration M ost common ocular finding in varicella M arked eyelid edema Conjunctival, Episcleral , and Circumcorneal conjunctival hyperemia C orneal edema Photophobia Treatment Acyclovir 800 mg po 5 times/day Famciclovir 500 mg or V alacyclovir 1 g P rednisolone acetate 1% instilled q 1 h for uveitis or qid for keratitis initially A tropine 1% or scopolamine 0.25% 1 drop tid.

58. Other viral infections Epstein-Barr virus Unilateral, multifocal, discrete anterior stromal infiltrates B ilateral , full-thickness, peripheral infiltrates have been reported in patients with and without a history of infectious mononucleosis Ringlike opacities Vascularization is a variable feature EBV has not been isolated from corneal tissue with documented stromal keratitis, and the mechanism of inflammation remains unclear There are reports of successful treatment using topical corticosteroids

59. Mumps ‘striate keratitis,’ described as lacy, linear opacities HTLV-1 has been reported to cause a bilateral, peripheral, anterior stromal IK that is chronic and steroid-unresponsive Measles are the causative organisms for IK

60. References Cornea Krachmer,Mannis,Holland Edn 2010 Parson’s Diseasesof the eye Edn 22

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