Interstitial keratitis, also known as stromal keratitis, is a non-suppurative inflammation of the corneal stroma that can be caused by both infectious and non-infectious diseases. It is characterized by cellular infiltration and vascularization of the corneal stroma with minimal involvement of the corneal epithelium or endothelium. Congenital syphilis is a classic cause of interstitial keratitis. Stromal keratitis associated with congenital syphilis typically begins between ages 5-15, presents bilaterally, and can lead to diffuse corneal inflammation, edema, and neovascularization if left untreated. Acquired syphilis less commonly causes unilateral stromal keratitis, which

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.  The 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. Drawing 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
 Keratitis 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 corneaAcute 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
o Anterior uveitis
Iridocyclitis commonly attends stromal keratitis and iritis can precede the onset of syphilitic
keratitis
o 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
Early 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
 Skeletal abnormalities
 Pneumonia
 Bullous 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),
 Keratitis
 Deafness
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
peripherallyand 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
 Enlarged lymph nodes
 Maculopapular rash over the trunk, palms, and soles
(mucous patches are infectious)
 Painless erosions of the mouth and rarely the conjunctiva
 Sudden hearing loss and
 Acute arthritis
Long-lasting stigmata of prior secondary syphilis may be subtle,
 Hypo- or Hyperpigmented spots on the skin
 Patchy 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

31. Treatment
Status Treatment
Infant with early congenital syphilis
Aqueous penicillinG 50 000 units/kg intravenously
every 8–12 hours for 10–14 days
Child (<12 years old) with late congenital syphilis
Aqueous penicillinG 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 penicillinG 2.4 million units (or 50 000
units/kg) intramuscularly once weekly for 3
consecutive weeks
Adolescent or adult with neurosyphilis
Aqueous penicillinG 3–4 million units
intravenously every 4 hours for 10–14 days

32.  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

33. 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

34. 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

35.  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

36.  Clinical manifestations
 Approximately half of patients with Cogan's syndrome present with typical and/or
atypical ocular symptoms,
 One-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

37. 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.

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

39. Factors differentiateCongenital Syphilis from Cogan's syndrome
 IK in congenital syphilis
 Insidious onset
 Limbal distribution,
 Corneal scarring
 Positive serologic tests and other systemic signs
 The IK of Cogan's syndrome
 Sudden onst
 Patchy distribution,
 Rarely 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

40. Diagnosis
 Leukocytosis
 Eosinophilia
 Elevated ESR
 Positive 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.

41. 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

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

43.  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

44.  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

45. 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

46.  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

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

48.  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
 Keratitis
 Uveitis
 Vasculitis
 Exudative retinal detachment
 Endophthalmitis

49.  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

50.  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
 Systemic antibiotic
 Ceftriaxone (Drug of choice)
 Azithromycin
 Doxycycline
 Tetracycline

51.  Parasitic Infection
 Acanthamoeba keratitis
o A history of contact lens wear and the use of homemade saline solutions
o 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.
o Although a superficial epitheliopathy is an early feature, stromal involvement ensues
with infiltration accompanied by edema, which is easily mistaken for herpetic stromal
disease.

52. o 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
o 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

53. Symptoms
 Severe pain (out of proportion to the degree of inflammation)
 Watering
 Photophobia
 Blepharospasm
 Blurred 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

54.  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)
Chlorhexidine
Others paromomycin , imidazoles such as fluconazole, itraconazole and miconazole
PK in non responsive cases

55. 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,
LatinAmerica,
Yemen
Travel to
endemic areas
Live microfilariae,
peripheral stromal edema,
centripetal full-thickness
stromal vascularization,
complete opacification,
absence of thinning
Features of Parasitic Interstitial Keratitis (IK) by etiology

56. 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
neovascularizatio
n, late thinning,
histologic findings
of organisms and
granulomatous
inflammation
African
trypanosomiasis
African sleeping
sickness
Trypanosoma
brucei (tsetse fly)
Africa
Travel to endemic
areas
Diffuse
neovascularizatio
n, severe scarring
and thinning,
potential
perforation
Microsporidiosis None Microsporidia Worldwide
Immunocomprom
ised status
Anterior to
midstromal
infiltration

57.  Viral Infection
 Herpes SimplexVirus (HSV)
Herpes simplex virus is a principal cause of corneal blindness manifest as
 IK
 nummular keratitis
 ulcerative necrotizing stromal keratitis
IK hallmarks of
 Edema
 New vessel formation
 Cellular infiltration
may be present to varying degrees and may be accompanied by scleritis and uveitis, which
further complicate this serious condition

58. Pattern of stromal infiltration may be
 Central or Peripheral
 Focal or Multifocal
 Superficial or Full thickness
o Wessely-type immune ring, if present, support the diagnosis
 Treatment
 Tab Acyclovir 400 mg BD
 Topical corticosteroids

59.  Varicella-zoster virus (VZV)
Herpes zoster is another common cause of IK
One of the many ocular manifestations of zoster is stromal infiltration
Most common ocular finding in varicella
 Marked eyelid edema
 Conjunctival, Episcleral, and Circumcorneal conjunctival hyperemia
 Corneal edema
 Photophobia
Treatment
 Acyclovir 800 mg po 5 times/day
 Famciclovir 500 mg or
 Valacyclovir 1 g
 Prednisolone acetate 1% instilled q 1 h for uveitis or qid for keratitis initially
 Atropine 1% or scopolamine 0.25% 1 drop tid.

60. Other viral infections
 Epstein-Barr virus
 Unilateral, multifocal, discrete anterior stromal infiltrates
 Bilateral, 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

61.  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

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