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
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
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
29.
30.
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