2. Definition
defined as discontinuation in normal
epithelium of cornea associated with
necrosis of surrounding corneal tissue.
3. Barriers of microbial infection
• Bony orbital rim, eyelids,
• Intact corneal & conjunctival
epithelium
Anatomical
• Tear film-mucus layer
• Lacrimal systemMechanical
• Tear film constitutes-IgA,
complement components, and
enzymes lysozyme, lactoferrin,
betalysins have antibacterial effect
• CALT
Antimicrobial
4. Normal defence system
Normal blinking and tear flow
mechanically washes out the organisms
Tear film contains lysozyme, lactoferrin,
betalysin which adversely affect the
bacteria
IgA binds to the organism and inhibits its
adherance to ocular surface
Components of complement pathway also
help.
5. Normal defence system
Squamous epithelium of conjunctiva
and cornea provides mechanical
barrier
Keratocytes secrete cytokines that
activate immune defences.
Langerhans cells are antigen
presenting cells in peripheral cornea
which activate T cells when foreign
antigens are processed.
CALT activate T cells and produce IgA
6. Risk factors- External
Trauma: causing breach in corneal
epithelium with concurrent inoculation
of organisms. Foreign bodies also can
cause bacterial keratitis.
Organisms that penetrate intact
corneal epithelium include neisseria
gonorrhea, meningitidis, c.diptheria,
hemophilus aegyptius,listeria species.
7. Risk factors- External
Contact lens wear: causes corneal hypoxia
and increased corneal temperature(1),
dereases pH, impaired tear exchange. it can
directly traumatise epithelium when eye is
rubbed with lens in place.
Extended soft contact lens wearers are at 10
to 15 times increased risk than daily lens
wearers(2).
Aphakic contact lens wearers have 6 to 9
times increased risk due to longer wear
intervals, reduced postop defence
mechanism of cornea or increased
hypoxia(3).
1 contact lens related k ulcers in compliant patients-Amj ohth 2004
2complications in patients with soft daily wear and soft extended wear-
CLAO J 1993
3Incidence of k ulcers in aphakic contact lens wearers england- arch
ophtalm 1991
8. Staphylococcal ulcer in a 70year old using
extended wear aphakic contact
lens...dense white well demarcated
stromal infiltrate with overlying epithelial
defect.
9. Risk factors- External
Smoking coupled with contact lens wear increases corneal
hypoxia.
Further contact lens case or its solution may be also infected
and infection may be occur... biofilm
Pseudomonas is the most common organism in contact lens
wearers, followed by staphylococcus sp and serratia
marcescens.
Intraepithelial
infiltration of the
cornea by
Pseudomonas
organisms in
a contact lens
wearer.
11. Risk factors- ocular surface
disorder
Pre-existing ocular diseases:
1. decreased corneal sensation
2. dry eye due to any cause
3. SJS and ocular burns
Lead to a disturbed precorneal tear film
thereby increases the chance of
adherance of microbes to corneal
epithelium.
12. Risk factors- bullous
keratopathy
Corneal endothelial decompensation
leads to surface abnormalities and
epithelial defects thereby
compromising the barrier function.
Risk also increases due to prolonged
use of local steroids and use of BCL.
Ulcerative keratitis developed in 4.7%
of patients with bullous keratopathy in
a study by Luchs et al.
13. Risk factors- topical
medication
topical steroid , antifungal therapy,
contaminated drops, traditional
medicines, aesthetics
Topical steroids affect the precorneal
tear film and local ocular immunity by
preventing neutrophilic migration in
response to chemokines released by
microbes. Also there is impaired
opsonization of bacteria. Corneal
superinfection has been reported after
indiscriminate use of steroids in acute
hemorrhagic conjunctivitis.
14. Risk factors- ocular surgery
Cataract, pterygium surgeries, LASIK, keratoplasty can be
complicated with occurrence of keratitis.
Mycobacteruim chelonei has been reported after LASIK in sporadic
and epidemic form4.
4-Infectious keratitis after LASIK;OPHTHALM2003- KARP CL, TULI SS, YOO SH, HUAN
15. Immunocompromised state
1. Diabetes (thickening of lamina densa
leading to EDs)
2. AIDS( candida keratitis)
3. Chemotherapy patients
4. SJS, burns patients, comatosed
5. Connective tissue disorders:
predispose to corneal melting and
causes secondary infectious keratitis.
Moraxella lacunata ulcers are associated
with alcoholics and debilitated patients.
18. Etiology
AEROBES ANAEROBES
1. GRAM POSITIVE COCCI 1. GRAM POSITIVE COCCI
A. Staph aureus
B. Staph epidermidis
C. Strep pneumoniae
D. Alpha and beta hemoltyic strep
E. Enterococcus
A. Peptococcus
B. Peptostreptococci
2. GRAM POSITIVE BACILLI 2. GRAM POSITIVE BACILLI
A. Bacillus cereus
B. Bacillus subtilis
C. Corynebacterium
D. Listeria monocytogenes
A. Actinomyces
B. Clostridium
19. Etiology
AEROBES ANAEROBES
3. GRAM NEGATIVE COCCI
A. Neisseria
3. GRAM NEGATIVE COCCI
Veillomella
4. GRAM NEGATIVE BACILLI
A. Pseudomonas aeruginosa
B. Acinetobacter
C. Azotebacter
D. Enterobacteria- klebsiella ,
serratia , proteus, escherichia
4. GRAM NEGATIVE BACILLI
A. Fusobacterium
B. Bacteroides
5. GRAM NEGATIVE
DIPLOCOCCI
Moraxella
Spirochaetales- treponema,
leptospira
6. GRAM NEGATIVE
COCCOBACILLI
Haemophilus
7. Acid fast bacilli- mycobacterium,
nocardia
20. Etiology
87% of bacterial keratitis have been
attributed to staph, strep, pseudomonas and
enterobacters.
Specific organisms:
1. Staphylococcal organisms: susceptible
corneas include prior herpetic infection, dry
eye, bullous keratopathy, previous ocular
surgery.
2. Streptococcus pneumoniae: cases of
chronic dacryocystitis.
3. Pseudomonas species: contact lens users,
use of contaminated fluorescein solution,
immunocompromised state.
21. Etiology
4. Gram positive bacilli- bacillus cereus:
keratitis following foreign body injury
5. Moraxella species:
immunocompromised states
6. Corynebacterium : C. Diphtherium
penetrates intact corneal epithelium.
C.xerosis is associated with moraxella
infection.
7. Actinomycetes :nocardia are found in
soil, seen foll trauma, canaliculitis
22. Etiology
8. Spore forming anaerobes: Clostridia found in
soil, cause keratitis rarely, may be associated
with air bubbles in corneal tissue or AC.
9. Nonsporing anaerobes: foll animal bites,
cause extensive tissue necrosis and gas
formation. Peptostreptococcus and
propionibacterium are common.
10. Non tuberculous mycobacterium: seen after
surgeries like laser-in-situ keratomileusis.
Mycobac leprae causes involvement of corneal
nerves.
11. Listeria monocytogenes causes suppurative
keratitis in animal handlers and farmers.
23. Parts of the ulcer
Base: surface on which the ulcer rests
Floor: exposed surface of the ulcer
Margin: junction between the normal
epithelium and ulcer
Edge: is the area between margin and
floor
24. Stages of corneal ulcer
1. Stage of infiltration:
Adherence of organisms to corneal
epithelium( facilitated by bacterial pili and
glycocalyx envelope in pseudomonas and
gonococcus)
Organisms produce cytokines and
chemokines which cause vasodilation
They also produce proteases and disturb
extra cellular matrix.
Subsequently necrosis begins depending on
virulence of org and host defence mechanism
If lesion does not involve BM it quickly heals.
If it extends beyond BM it progresses.
25.
26. 2. Stage of progression:
Active ulceration results from necrosis and
sloughing of epithelium, BM, stroma due to
lytic enzymes released.
The corneal lamellae imbibe fluid and project
above the surface giving saucer shaped
appearance to it. Sides and floor of the ulcer
show grey infiltration
Vascular congestion of conjunctiva, iris and
ciliary body results in hypopyon.
Further progression may result in
descmetocoele and perforation due to
thinning of cornea.
27.
28. 3. Stage of regression:
Induced by natural host defence
mechanism
Improvement is seen in clinical signs
Line of demarcation forms around the
ulcer consisting of leucocytes that
phagocytose the offending organism and
tissue debris
Margin of the ulcer becomes smooth ad
floor more transperant
Superficial vascularisation increases the
cellular and humoral immunity
Ulcer begins to heal.
29. 4. Stage of cicatrisation:
Epithelial regeneration continues- histiocytes
and keratocytes convert to fibroblasts
Under the epithelium granulation tissue is
formed by fibroblastic proliferation. Fibrous
tissue is laid down and deposited until
curvature of the cornea is achieved.
When healing is complete, vessels regress
and become ghost vessels.
Degree of scarring results in opacities which
can be nebula, macula or leucoma.
Gross degree of refraction in the area of scar
is due to criss cross laying down of fibrous
tissue.
30.
31. Clinical features
Clinical signs and symptoms are variable depends on the
virulence of the organism
duration of infection,
pre-existing corneal conditions
immune status of host
previous use of local steroids/anti microbials
32. Symptoms
1. Pain : superficial ulcers are more
painful than deep due to sensory
supply. Sudden relief of pain may
suggest perforation.
2. Redness and photophobia are
associated symptoms. Associated
conjunctivitis may cause redness in
gonococcal, pneumococcal and
hemophilus infections.
33. Symptoms
3. Discharge : watery discharge is
usually due to a viral ulcer, but a small
bacterial ulcer may cause reflex
tearing. gonococcus causes
mucopurulent discharge.
Pseudomonas is asso with greenish
yellow discharge. Corynebacterium
dipth causes membranous discharge.
34. Symptoms
4. Decreased visual acuity: central
corneal ulcers esp pseudomonas and
staphylococcus have significant loss
of visual acuity. Other factors
contributing: pupillary membrane,
hypopyon, cataract, glaucoma, vitritis.
Vision is not decreased in peripheral
ulcers like coagulase negative staph.
35. Onset of the disease
Sudden onset of decrease vision,
pain, photophobia is seen in staph,
pseudomonas and pneumococcus
species.
However bacteria like moraxella,
coagulase neg staph, nocardia
keratitis have gradual onset and
indolent course.
37. Ocular examination
1. eyelids:
Trichiasis
Coloboma
Entropion, ectropion
Proptosis
Lagophthalmos
Blepharitis
Evert and see for foreign body
38. Ocular examination
2. lacrimal sac: rule out dacryocystitis.
3. conjunctiva: associated conjunctivitis
with gonococcal, pneumococcal and
hemophilus may be present.
Presence of chemosis amd
pseudomembranes to be recorded.
Circumciliary flush may be seen in
bacterial ulcer.
Type of discharge to be noted-
mucopurulent in bacterial. Greenish in
pseudomonas.
39. Conjunctival vs ciliary congestion
S.
no.
Feature Conjunctival
congestion
Ciliary congestion
1. Site More marked in the
fornices
More marked around
the limbus
2. Colour Bright red Purple or dull red
3. Arrangement of
vessels
Superficial and
branching
Deep and radiating
from limbus
4. On moving
conjunctiva
Congested vessels
also move
Congested vessels
do not move
5. On mechanically
squeezing out
Vessels fill slowly
from fornix towards
limbus
Vessels fill rapidly
from limbus towards
fornix
6. Blanching, i.e., on
putting one
drop of 1 in 10000
adrenaline
Vessels immediately
blanch
Do not blanch
40. Ocular examination
4. Precorneal tear film: in active keratitis, tear film will
have numerous cells and debris.
5. cornea:
Corneal ulcer - location, shape, margin, size,
epithelial defect, infiltration, sensations
Surrounding cornea and vascularisation
41. Corneal ulcer
1. location: should be marked
schematically on diagram.
May be central, paracentral,
peripheral or total.
Central ulcers have poor vision with
poor visual prognosis- usually
staphylococcal.
Mycobacterium cause peripheral
ulcers.
42.
43. Corneal ulcer
2. Shape of the ulcer: bacterial are
usually punched out ulcers; round or
oval in shape
3. margins: vary according to the stage.
Healing ulcers have well defined slopy
margins.
Active ulcers have indistinct/ragged
margins.
44.
45. Corneal ulcer
4. Size of the ulcer: important for follow up
visits and monitor progress.
5. Epithelial defect:
Epithelial defect and size of infiltration
should be measured separately in two
largest meridians.
In cases of corneal abscess, epithelium
may be intact over the infiltration.
Staining may be used ( fluorescein or rose
bengal) whenever necessary.
Epithelial edema if present should be
noted.
46.
47. Corneal ulcer
6. infiltration: may be single or multiple,
should be measured.
7. Corneal sensations: either with a
cotton wisp or esthesiometer.
48. Surrounding cornea
May be clear or hazy
Pseudomonas ulcers – surrounding
cornea is edematous and appears like
a ground glass.
Clearing of surrounding edema may
be a sign of healing.
51. Superficial corneal
vascularisation
Deep corneal vascularisation
Vessels can be traced from limbus
into conjunctiva
Vessels end abruptly at the limbus
Vessels are bright red and well
defined
Vessels have a bluish red blush
They branch in arborescent
manner
Run parallel to each other
Make the corneal surface irregular Donot disturb the corneal surface
52. Ocular examination
6. Anterior chamber: mild cells, flare or gross
hypopyon(measurement) may be present.
Mobile hypopyon is seen in bacterial keratitis i.e.
Movement of hypopyon with change in head
position of the patient.
Hypopyon is fluid and settles at 6oclock. Horizontal upper
border. Shifts on head tilt. Absorbs readily and recurs
53. Ocular examination
7. iris: synechiae, rubeosis iridis, in a
perforated ulcer- corneoiridic plug.
8. Pupil and lens: pupil size and
reaction; lens if visible for cataractous
changes.
9. Scleral involvement: scleral
involvement warrants the use of iv
antibiotics.
54.
55.
56. Grading of corneal ulcer
Harrison SM. Grading corneal ulcers. Ann Ophthalmol 1975;7:537-9, 541-2.
Features Mild Moderate Severe
Size <2mm 2-5mm >5mm
Depth of
ulcer
<20% 20-50% >50%
Stromal
infiltrate
1.Density
2.Extent
Dense
Superficial
Dense
Upto mid-
stroma
Dense
Deep stromal
Scleral
involvement
present
57. Ocular examination
10. Posterior segment: vitreous and
retina if visible for vitritis.
11. IOP: digital;
in cases of descematocoele, never
assess digitally.
59. Special features-
staphylococcus
2 types of staphylococci keratitis
1. Accompanies staphblepharitis or conjunctivitis –
inflammatory response to toxins produced by organism
in lids and conjunctiva, one or more, small, well
circumscribed, anterior stromal infiltrates that are free
of replicating bacteria.
2. Inflammatory response to staphylococci within cornea.
Infiltrate is central, longer, severe.
60.
61. Staphylococcal
• Hallmark of staphylococci
diseases is suppuration
Central,oval, opaque
Distinct margins.
Mild oedema of remaining
cornea.
Stromal abscess in
longstanding cases.
Mild to moderate AC
reaction.
Affects compromised
corneas e.g. Bullous
keratopathy , dry eyes ,
atopic diseases.
62. Pseudomonas
P. aeruginosa, P. flurescens (less frequent)
P. aeruginosa is a slender, gram negative rod, synthesize
a bluish green phenazine pigment (pyocyanin) therefore
the colour green.
Known to replicate in any moist area; grows in eye
drops, irrigating solutions, cosmetics fluorescein
solution.
Has hemolysins, lipase and proteases
63. Pseudomonas
Rapidly spreading.
Extends periphery & deep
within few days.
Stromal necrosis & corneal
liquifaction progressing to
destruction of stromal
descemetocoele and
perforation
Spreads concentrically and
symmetrically to involve
whole depth of cornea-Ring
ulcer.
Greenish-yellow discharge.
Hypopyon is present.
Untreated corneal
melting.
64. Streptococcus Pneumonia (pneumococcus)
Are encapsulated, gram positive, lancet shaped
diplococci, seen as short chains
Survive as long as it is extracellular. Once ingested, it is
destroyed. Protection against phagocytosis is prevented
by capsule.
Produces several toxins of which Pneumolysin causes
corneal destruction
Common if coexistent chronic dacryocystitis present
65. Pneumococcal
Ulcer serpens is greyish
white or yellowish disc
shaped ulcer occuring
near center of cornea.
starts at periphery &
spreads towards centre
Tendency to creep over
the cornea in serpiginous
fashion- Ulcus Serpen.
Violent iridocyclitis is
often associated with it.
Hypopyon – always
present
It has great tendency for
PERFORATION.
66. Streptococcus viridans
Infectious crystalline
keratopathytype of
stromal keratitis
Characteristic: infiltrate
with lattice configuration in
anterior stroma.
67. Infectious Crystalline Keratopathy
The arborising profile of the infiltrate is believed to
reflect, proliferation of bacterial colonies along lamellar
planes of stromal collagen.
relative absence of associated inflammatory response.
May be associated with ED or not
Infiltrates are also described near graft host junction of
cornea transplant & after incisional keratotomy in
cornea grafts.
68. Infectious crystalline keratopathy
Risk factors include:
a) Suture in situ
b) Loose sutures
c) Prolonged use of local steroids
d) Use of contact lens
e) Epikeratophakia
f) h/o HZV/HSV
g) Abuse of topical anaesthetic agents.
69. Infectious Crystalline Keratopathy
Stromal involvement is in
form of neovascularisation,
scarring, ring abscess or
combination.
Paucity of inflammation is
due to local
immunosupression
Histopathology: colonies of
basophilic bacteria in
anterior stroma (colonies
are insinuated between
collagen lamellae with
paucity of inflammatory
cells)
70. BACILLUS
Bacillus Cereus keratitis is extremely severe and can
progress rapidly to perforation, endophthalmitis.
c/f: ring infiltrate is seen in stroma.
H/o FB/ trauma is usually present
71. CORYNEBACTERIUM
Can penetrate intact cornea epithelium
Rare due to immunization
Small ED with underlying stromal infiltrate
Frequently associated with moraxella infections
MORAXELLA
Seen in immune compromised
Ulcer is oval, seen on inferior exposed part of cornea
infiltrate spreads deeply into the cornea, forming a stromal
abscess
The ulcers are ofter, painless, but almost invariably cause
a hypopyon and ocassionally a hyphema
72. LISTERIA
Ocular involvement is rare.
Can penetrate intact corneal epithelium
Clinically large KPs, elevated iop, dark hypopyon and
pigment dispersion noted.
Outcome poor.
NOCARDIA
Seen usually in the immunocompromised
Preceeded by minor trauma
Associated conjunctivitis may be there
Non specific punctate epitheliopathy
Stromal involvement is nodular
or granular
Satellite lesions may be present
73. ACTINOMYCES
Anaerobe, rare cause of keratitis
Chronic granulomatous infection
Asso with canaliculitis
May also have head face neck
involvement
Ulcer bed is relatively dry looking,
discrete white stromal infiltrates are
seen, satellite lesions may be present(
mistaken for fungal)
74. DEPENDING UPON THE
CIRCUMSTANCES, THE COURSE OF
THE BACTERIAL ULCER MAY TAKE
ONE OF THE 3 FORMS:-
A.ULCER MAY HEAL & BECOME
LOCALIZED.
B.PENETRATE DEEP LEADING TO
CORNEAL PERFORATION.
C.SPREAD FAST IN THE WHOLE
CORNEA AS A SLOUGHING
CORNEAL ULCER.
77. Corneal Opacity
Nebular cornea opacity : details of iris are seen through the
opacity.
Macular cornea opacity : more dense details of iris not seen
but iris and pupillary margins are visible.
Leucoma : dense white opaque cornea. No new of Iris/Pupil.
Old central leucomata sometimes show a horizontal
pigmented line in palpebral aperture (nature is obscure may be
due to deposition of iron from pre corneal tear film)
78.
79. Corneal opacity
thin diffuse nebula interferes more with vision than
dense localized leucoma (not in pupillary area) because
leucoma entirely blocks light but nebula refracts light
irregularly causing blurring of image.
Small central or paracentral opacity does not prevent
focusing of image on macular region of retina hence is
loss of brightness rather than of definition
Some opacity always remains when bowmans
membrane is injured but clears considerably in younger
individuals.
80. Keratectasia/ectatic cicatrix
In case of deep ulcers, loss of tissue causes thinning of
entire cornea so that it bulges under the normal IOP.
as the cicatrix becomes consolidated, the buldging
disappears or remains permanently as ectatic cicatrix.
81. Descemetocoele
Ulcers especially those due to pneumococci extend
rapidly in depth so that the whole thickness of cornea
except DM may be destroyed.
DM offers great resistance to inflammatory process but
is unable to support the IOP and hence herniate through
the ulcer – Keratocoele
this may persist surrounded by a white cicatricial ring
or may rupture.
82. PERFORATION
Causes : sudden exertion by patient like coughing/
straining/ sneezing, causing increased IOP.
Rupture of descematocoele
escape of aqueous
IOP falls to atmosphere level
Iris & lens is driven anteriorly to touch cornea
Effects of perforation :
IOP falls
Pain decreases
extension of ulcer ceases
cicatrization starts rapidly
83. Perforation
After perforation, iris is drawn into the aperture when
aqueous escapes.
If perforation is small, iris adheres to the opening, scar
tissue is formed over adherant iris – pseudocornea
(anterior synechiae)
If perforation is large, there occurs prolapse of iris.
Colour of iris becomes obscured soon by deposition of
grey or yellow exudate on its surface but eventually iris
stroma becomes thinned and black pigmentary
epithelium becomes visible
84. Secondary Glaucoma
Exudates clog the trabecular meshwork
If prolapse of iris has occurred, exudates covering the
prolapse becomes organized and forms thin layer of
connective tissue over which the epithelium grows.
Contraction of the fibrous tissue tends to flatten the
prolapse
85. STAPHYLOMA
An ectatic cicatrix in which the iris is incarcerated which
may be partial or total.
Bands of scar tissue vary in breadth & thickness –
lobulated appearance often blackened with pigment,
hence the name.
Histology: iris tissue enmeshed in corneal tissue
remnants (hence also called corneoiridic scar)
86. Anterior Capsular Cataract
If perforation occurs opposite pupil pupillary margin of
iris becomes adherent to the edges of cornea ulcer and
aperture becomes filled with exudates.
Anterior chamber is reformed very slowly, if lens
remains in contact with ulcer for long time – anterior
capsular cataract may be formed.
87. Corneal fistula
As the Anterior chamber reforms, the exudate filling the opening is
submitted to strain & frequently ruptures if patient is restless. If this
process is repeated, opening becomes permanent forming a cornea
fistula.
When whole cornea sloughs with the exception of narrow rim at the
margin, total prolapse of iris occurs.
Pupil usually becomes blocked with exudate & a
false/pseudocornea is formed consisting of iris covered with
exudate.
88. Expulsion of lens & Vitreous
If perforation takes place suddenly the suspensory
ligament of lens is stretched or ruptured, causing
subluxation of lens or even anterior dislocation &
spontaneous expulsion of lens & vitreous through the
perforation.
89. Hemorrhage
With perforation, sudden reduction of IOP may cause
rupture of blood vessels causing intraocular hemorrhage
(vitreous/choroidal/choroidal/subretinal/subchoroidal)
Expulsive hemorrhage may also occur.
90. Others
Finally organisms causing the ulceration may gain access
to the interior of eye following perforation causing
Endophthalmitis
Panophthalmitis.
91. Ocular Investigation
Apart from slit lamp examination, ultrasonography
Bscan should be done if endophthalmitis is
suspected.
93. Microbiological Investigations
Detection of bacteria, fungi, protozoa
Corneal scrapings are to be collected & sent for
Gram /KOH staining
Culture /sensitivity
Contact lens, lens case & solution should be
evaluated in lens users.
94. Collection of samples
Anaesthesia: Under topical anaesthesia
Instill 2 drops of 0.5% proparacaine in the lower
fornix
Proparacaine is least bactericidal as compared to
tetracaine & xylocaine.
Sedation in children, uncooperative patient
95. Collection of sample instruments
Kimura’s spatula
26 G needle
Bard Parker Blade
Hypodermic needle
Platinum spatula (rapidly sterilized with a Bunsen
Burner) (traditional)
96. Corneal scrapings - technique
Lid speculum (apply gently)
Scraping should ideally be done under slit
lamp/operating microscope.
Any debris around the ulcer should be cleaned with
a sterile swab.
97. Corneal scrapings - technique
Using kimura’s spatula/23 G needle /Bard Parker
knife, the leading edges & base of the ulcer are
scrapped.
Streptococcus is found at the edge, Moraxella is
found at the base
Avoid touching eyelids/eyelashes to prevent
contamination.
98. Corneal Scrapings
More recently, Calcium Alginate Swabs moistened with
trypticase Soy broth is used for collecting corneal
specimens.
Studies have demonstrated higher yield of bacteria &
fungi when this method was used as compared to
platinum spatula.
Comparison of techniques for culturing corneal ulcers
ophthalm 1992
99. Difficulties – Sample collection
Insufficient material to inoculate in small ulcers
In advanced cases of descematocoeles
prior use of antibiotics gives false results
In deep stromal keratitis, overlying epithelium is
intact, in this case small trephine/microsurgical
scissors may be used to obtain the sample
100. SMEARS
Transfer material from spatula to glass slide &
spread over 1cm area
Mark the area with wax pencil to obviate the need
to search for the area of scrapings.
Minimum 2 slides – gram & KOH stain. Additional
smear is prepared if indicated for other stains.
101. Gram staining – Method
1. Fix smear either by placing slide in methanol for 5-10
minutes & air dry OR pass the slide through flame 2-3
times, allow cooling.
2. Flood the slide with Gentian violet for 1 minute.
3. Rinse with tap water
4. Floor the slide with Gram’s iodine solution for 1 minute
5. Rinse with tap water
6. decolorize with decolorizer solution
7. Rinse with water
8. Flood the slide with counter stain – safranin for 30
seconds
9. Rinse with water
10. Allow to dry.
102. RESULTS
Identifies 75% of the times
Gram positive organisms take up violet iodine
complex & stain blue-purple
Gram negative bacteria lose the gentian violet
iodine complex when decolorized & stain pink with
safranin.
105. GIEMSA Staining
Romanowsky type stain which uses eosin,
methylene blue & ozide dyes
It stains the DNA/RNA, cell wall & septations do not
take up the stain.
Helps differentiate bacteria (blue) from fungi
(purple), stains chlamydia inclusion bodies & cysts
trophozoites of Acanthamoeba
106. KOH wet mount
Scraped material is spread out on glass slide
One drop of 10% KOH is put on scrapings &
covered with cover slip & examined under
microscope.
KOH helps in loosening stromal lamellae &
exposing fungal filaments.
Stains filaments light yellow.
Identifies fungi & acanthamoeba.
90% sensitive.
107.
108. Ziehl Neelson Acid Fast Stain
Principle: acid fastness has been ascribed to high
content & variety of lipids, fatty acid & higher alcohols
found in tubercle bacilli
Integrity of cell wall
Procedure:
Make smears, air dry & heat fix them.
Flood smear with carbol fuschin.
Keep it for 5 mins with intermittent heating.
Wash with water & pour 20% H2SO4 on the smear,
keep for 2 mins.
Wash again & pour loefflers methylene blue for 30 sec.
109. Ziehl Neelson Acid Fast Stain
Wash slide & air dry smear.
Examine under oil immersion, objective of 100x
Appearance of Organisms:
Pink rod against blue background (background varies
with counter stain used)
Interpretation:
Smear should be considered negative after examining
100 fields taking about 10mins
110. CALCOFLUOR White Stain
Calcofluor binds to chitin & cellulose therefore
organisms like yeast & filamentous fungi stain
bright green white Calcofluor under epifluorescent
microscope.
Cysts of Acanthamoeba also stain bright green,
trophozoites of acanthamoeba stain reddish –
orange.
111. ACRIDINE ORANGE
Chemofluorescent dye – stains fungi & bacteria
yellow orange against a green background
Identifies gram positive and negative bacteria &
yeast as well as hyphal forms of fungi &
acanthamoeba.
113. Modified Grocott Gomori Methenamine-
Silver Nitrate stain
reliability is more than Gram/KOH for fungal
infections
Specimen should be spread on gelatin coated
slides.
Fungus cell wall & septa stain black against faint
green background.
114. Culture Media
Media Organisms
1) Blood Agar Aerobic bacteria/fungi
2) Chocolate Agar Aerobes – facultative anaerobes
Neisseria
Hemophilus
Moraxella
3) Thioglycolate broth Aerobic & Anaerobic bacteria
4) Sabouraud’s Dextrose Agar Plate with
Antibiotic (*)
Fungi
Nocardia
5) Brain heart infusion Broth with Antibiotic (*) Fungi
Nocardia
6) Cooked meat Broth Anaerobic Bacteria
7) Thayer Martin Blood Agar plate Neisseria
8) Lowenstein Jensen Media Mycobacterium
(*)Work at room temperature, (rest work at 35 c)
115. Culture media
initial procedure should be obtaining
culture material from the conjunctiva and
lid margins of both eyes
the entire lower cul-de-sac should be
wiped, The upper and lower tarsal
conjunctivae and all of the material
obtained is placed directly into culture
The upper and lower lid margins also
should be cultured and placed on the same
plates used for the conjunctival specimens
116. TECNIQUE FOR CULTURE
Apply topical Anaesthetic
Scrape the margin of ulcer with kimura’s spatula.
Transfer the isolate directly to the culture plate by
making a row of C shaped marks, reversing the edge of
spatula with each C, so that all the material from spatula
is transferred to the plate.
For inoculation into liquid media, the spatula is briefly
immersed directly into the culture fluid.
117. Micro - ARD
Micro – antimicrobial removal device.
In cases which have been treated with antibiotics,
microARD is used to yield positive cultures.
It has sterile RESINS which bind to antibiotics.
In a study by osato et al, use of micro ARD increased the
isolation of organisms from 88% to 100% in ocular
infections.
118. Duration of Isolation
Usually 48 hours.
All plates to be examined daily with the help of
microscope & liquid media to be evaluated for presence
of turbidity.
Growth outside C-streak should be disregarded (implies
contamination)
Indigenous organisms in tear film may appear-should be
distinguished on basis of sparse growth & isolation of
the same organism from ipsilateral lids/conjunctiva.
Aerobic cultures of corneal of specimens should be kept
for 7 days; an aerobic for 7-14 days; Mycobacterial &
fungal for 4-6 weeks before being reported as no
growth.
119. AntiMicrobial Susceptibility Testing
Minimal inhibitory concentration (MIC) : lowest
concentration of antibiotic that will inhibit visible
growth of micro organism after overnight incubation.
Other tests:PCR
120. CONFOCAL MICROSCOPY
Useful when infecting organism is large (>15m) like
acanthamoeba, filamentous fungi, microsporidia,
Borrelia keratitis.
Is shows the cysts & trophozoites of acanthamoeba,
enlarged cornea nerves.
Filamentous fungi are seen as numerous high contrast
lines.
121. CORNEAL BIOPSY
In case of deep mycotic keratitis/intrastromal abscess –
staining & culture comes negative.
In such cases, a diagnostic superficial keratectomy or
corneal biopsy is necessary.
Performed under topical anesthesia under operating
microscope.
A microtrephine is advanced into the anterior corneal
stroma to incorporate both the infected & clinically
normal 1mm rim. Avoid visual axis. A crescent blade or
bard parker knife is used to undermine the tissue, which
may then be cut with microscissors & the tissue excised
with fine tooth forceps (do not crush)
122. Treatment
Aims of Rx:
1. Eliminate viable bacteria from the cornea.
2. Suppression of inflammatory response.
Protein binding results in reversible inactivation of antibiotics
( protein bound antibiotic has No or little antibacterial activity.
Albumin is present in debris of cornea ulcer, adjacent for nices
& in aqueous humor of inflamed eyes.
Studies insufficient.
123. Routes of Administration
Aggressive antibiotic therapy
A. Topical
B. Periocular
C. Systemic
D. Others.
124. TOPICAL
Most effective (produces high concentration locally and
lower in systemic)
No systemic toxicity
Not just antibiotic but also has cleansing effect by washing
bacteria, inflammatory cells, destructive enzymes & debris.
Until microbiological diagnosis is established, start broad
spectrum antibiotics at frequent intervals.
Use either commercially available formulations or fortified.
Fortified eye drops can be kept at room temperature for week
without loss of activity.
Initially, antibiotics are to be instilled hourly (every half an
hour yields higher corneal drug levels, but compliance is
erratic.
125. TOPICAL
When confronted with a severe ulcer (particular gram
negative suspect), antibiotic instillation at 1 minute
intervals for 5 doses each hour for the first 6-8 hours is
recommended, followed by hourly instillation. (used not
more than 8 hours because potential toxicity is not
known)
PetitTH : Management of cornea ulcers : Symposium
on ocular Therapy, volume 8, New York, John Willey &
Sons 1976.
126. TOPICAL
When clinical evidence of improvement seen, treatment
is limited to working hours (hourly administration &
ointment at night)
With additional signs of healing, frequency is decreased
to 2 hours then to 3 hours intervals & so forth.
With increasing signs of healing, fortified preparation
can be substituted by commercially available drops.
127. ANTIBIOTICS
Recently, commercially available fluoroquinolones are
broad spectrum (gram positive, gram negative,
penicillinase producing & methicillin resistant Staph)
In a study done, they have found that 0.3% ciprofloxacin
eye drops given hourly causes mean corneal tissue levels
exceed the minimal inhibitory concentration for most
corneal pathogen.
Superior penetration of cornea by ofloxacin is offset by
greater potency of ciprofloxacin.
128. TOPICAL ANTIBIOTICS
2 multi centric studies have shown that a single topically
administered fluoroquinolone is as effective as 2
fortified antibiotic preparations.
Commercially available preparation have advantages :
a) No frequent preparation
b) Superior stability at room temperature
c) Fewer potential toxic side effects.
129. PERIOCULAR INJECTION
Either subconjunctival or subtenons produce higher corneal
drug levels than topical
lesser risk of systemic toxicity than systemic form.
Side effects include greater patient apprehension, more pain,
inadvertent intraocular administration.
Comparative evaluation of periocular versus topical difficult
because:
a) Different quantity of drugs
b) Arbitary selection of frequency
c) Variable status of corneal epithelium in ulcer
130. PERIOCULAR ANTIBIOTICS
Can be used when
Confronted with a gram negative extensive cornea ulcer not
responding to topical therapy.
Infiltrates extending beyond limbus involving sclera.
Periocular therapy is always in addition to topical & never
sole source of treatment. Discontinue when signs of
improvement come & continue topical.
Periocular injection is very powerful in a already inflamed
eye. Hence 5 topical doses of 0.5% proparacaine at 2 minutes
interval is recommended before the injection OR 0.2 ml of
2% lidocaine can be given subconjunctivally in the same
quadrant as antibiotic will be given.
Give upto 1ml of injection, ballooning the bulbar conjunctiva
adjacent to the limbus in the meridian closest to the ulcer.
131. SYSTEMIC ADMINISTRATION
Risk of generalized toxicity higher.
Concentration of drug reaching aqueous humor following
systemic administration is less than that resulting from local
therapy.
consider it only in cases of
a) Scleral involment;
b) Suspected endophthalmitis.
132. OTHER MODES:
Of historical interest continuous antibiotic lavage either via a
catheter passed through upper lid or infusion contact lens
device.
Corneal Collagen Shield:-
originally developed as a therapeutic bandage lens, in shape
of contact lens from purified porcine scleral tissue or bovine
corium & stored in dehydrated state.
If rehydrated in a solution containing antibiotic, collagen
shield absorbs variable quantity of the drug. Following
application to the eye, proteases degrade the collagen & the
device fragment dissolves.
Dissolution time : 12-72 hours (varies with manufacturing
process)
133. CORNEAL COLLAGEN SHIELD
Studies show it is equal in efficacy to topical therapy.
Best used as a supplement of enhancing cornea drug
levels in irresponsive cases.
134. TRANSCORNEAL IONTOPHORESIS
Direct current to drive an ionized drug through the
cornea epithelium into the stroma & aqueous.
A cylindrical eye cup containing the drug is placed on
the eye & circumscribes the limbus.
An electrode with the same charge as the drug contacts
the drug in the eye cup, a 2nd electrode of opposite
charge is connected to the ear.
A milliampere direct current maintained for 1-10
minutes overcomes surface resistance of cornea
epithelium & drives the drug into stroma & aqueous.
Experimental.
135. SPECIFIC ANTIBIOTICS
Ideally selection should be based on culture sensitivity
If no bacteria are seen or staining, decision to be taken
between 2 most common bacteria that is Staphylococcus
& Pseudomonas
In case of Staphylococcus, use a drug that is effective
against Penicillinase producing Staphylococcus. Routine
coverage of Pseudomonas is advised because of its
prevalence & also because of the rapidity with which it
destroys cornea.
Negative gram staining in case of clinically diagnosed
bacterial ulcer, we begin with gram positive cover (5%
cephazolin) & gram negative cover (1.4% Tobramycin
or Gentamicin)
136. Cefazolin :- 50mg/ ml
Powder form: 500mg from 10ml artificial tears, take 5cc &
solubilize the powdered contents.
Transfer 5cc of this to the bottle of artificial tears making it
500mg/10ml.
Excellent activity against staphylococcus & streptococcus.
137. BACITRACIN
Can replace cefazolin if patient is sensitive to peicillins
Bacterial resistance is low since it less commonly used.
Causes discomfort when instilled.
Concentration : 10,000 units/ml
Preparation : take 15ml bottle of artificial tears, remove
9ml of artificial tears & add to each of three vials of
sterile bacitracin powder (50,000 u/vial). Return the 9ml
of solubilized bacitracin to artificial tear Bottle. This will
give 1,50,000 units/15ml.
138. VANCOMYCIN
Agent of choice for treatment of gram positive
organisms that do not respond to cefazolin/bacitracin.
Concentration 50 mg/ml
Preparation:
Remove 3ml from 15ml artificial tear bottle & discard.
Vial of vancomycin : 500mg
Solubilize 2 vials with 2cc of sterile water each: (total
4cc). Add 3ml (1 & half vial) into the artificial tear
bottle to make 750 mg/15ml.
Not for routine use to prevent resistance.
139. FLUOROQUINOLONES
Commercially available (ciprofloxacin/ Ofloxacin /2nd
gen), Levofloxacin – 3rd gen, Gatifloxacin/moxifloxacin
– 4th gen
Clinical studies have proven efficacy equal to that of use
of 2 drugs.
140. Organism Recommended Alternative
No organism Cetazolins +
Tobramycin OR
fluoroquinolone
Bacitracin +
Gentamicin
Gram Positive Cocci Cefazolin Bacitracin
Vancomycin
Gram Negative Cocci Cefazolin Fluoroquinolone
Fortified Ceftriaxone
(+systemic therapy)
Gram negative diplobacilli Cefazolin or
fluoroquinolone
Fortified Ceftriaxone
Gram negative bacilli Tobramycin or
fluoroquinolone
Gentamicin
141. SPECIFIC ANTIBIOTIC
After culture sensitivity report comes in 48 hours
therapy can be modified.
If lab report indicates that the treatment in progress will
not be effective, yet the ulcer is responding well,
disregard the report & observe.
As a conservative guideline antibiotics can be
discontinued safely 7-10 days after the corneal infiltrate
has cleaned & epithelial continuity has been restored.
In cases of Pseudomonas, small numbers of viable
bacteria may persist in the cornea, & recommence has
been described despite effective antibiotic therapy for
appropriate length of time therefore continue them for 3-
4 weeks or even after the infiltrate tears.
143. CORTICOSTERIOIDS
Termination of bacteria does not result in cessation of
inflammation.
PMNL cause stromal destruction.
Topical steroids have to be considered when
inflammation involves central or paracentral cornea.
Risk: steroids impair phagocytosis & inhibit killing of
bacteria therefore balance to be struck between desirable
& undesirable effects of steroids.
144. STEROIDS
Study: effect if topical steroids on antibiotic treated bacterial
ulcer : Arch ophthalm 98: 1980 proved that addition of topical
steroids to an EFFECTIVE BACTERICIDAL drug does not
enhance bacterial replication if steroid is not instilled more
frequently than antibiotic.
In practice however, bacterial keratitis is treated solely with
antibiotics.
Only when positive Therapeutic response is seen, steroids can
be added.
Commonly used : 1% Prednisolone acetate suspension with
lesser frequency than antibiotics & tapered.
145. CYCLOPLEGICS
Long acting Parasympatholytic
Mydriatic
Cycloplegic
Atropine 1%
Homatropine 1%
Dose: TDS or QID
Action – defers formation of posterior synechiae and reduces discomfort
caused by Ciliary muscle spasm.
IOP to be treated with antiGlaucoma (0.5% Timolol or Acetazolamide)
NSAIDS are best avoided as they may cause increased chances of
corneal melting
ARTIFICIAL TEARS
146. CONTACT LENS
When stromal necrosis results in substantial tissue loss
with thinning the diseased cornea is subjected to trauma
by li margins from blinking & to desiccation due to
abnormal tear distribution due to irregular surface.
Both factors can increase inflammation & lead to
perforation.
Soft contact lens over the cornea can interrupt this cycle.
It also facilitates reepitheliazation & promotes
fibroblastic proliferation.
But is may act as a physical barrier to the topical drugs,
hence dose of antibiotics should be increased.
147. CONTACT LENS
In most severe cases, when entire thickness of cornea
stroma has become Necrotic & slough & only DM is
intact, hydrophilic contact lens is useful.
Provides structural reinforcement of DM.
No well documented evidence for use of collagenase
inhibitors in treatment of bacterial keratitis.
148. OTHERS
trimming to be done in all cases.
If chromic dacryocystitis is present, DCT needs to be
done.
If chronic marginal Blepharitis treat MG dysfunction.
149. Monitoring
Slit lamp examination to be held every 12 hours during early phase.
once clinical response is established, once a day.
Signs of healing
a) Decrease/clearing of hypopyon
b) Decrease conjunctival discharge/debris
c) Decrease in AC reaction
d) Sloping edges/healing of ED
e) Increased response of pupil to mydriatic
f) Vascularisation occurs.
Resolution of corneal edema/infiltrates takes time.
Never patch an eye with cornea ulcer: closure of lids increases
temperature is cul-de-sac & discharge accumulates helping
bacterial replication.
150. Surgical Management
Removal of necrotic material may be hastened by repeated
scraping of the ulcer floor with spatula.
Cauterization:
pure carbolic acid (100%) or trichloracetic acid (10-20%)
Carbolic acid penetrates little deeper when applied thus acting
more widely (caustic & antiseptic)
Contraindicated in ulcers with extensive thinning or perforated
ulcers.
Acid must not touch the conjunctiva lest adhesions form
between lids & globe.
Povidone – Iodine 5% can be alternative.
151. Surgical Management
Intravitreal injection of antibiotics vitreous tap if
endophthalmitis is proven or Bscan
Treatment of Perforated Ulcer:
A. In case of small perforation over the iris, adherant leucoma is
formed & anterior chamber reforms no special treatment
required.
B. If perforation fails to heal & AC remains flat with hypotony:
a) Less than 2mm in size, use of tissue adhesive like N-butyl 2-
ethyl cyanoacrylate monomer or fibrin glue is used to seal it.
152. Cyanoacrylate glue
Applied to the area of perforation after careful debridement. The
surface is dried with a sponge & a small drop of tissue adhesive
from the undersurface of a bent iris repositer or a hypodermic
needle is placed immediately over the perforation. Drying takes 5-
10 minutes after which anterior chamber reforms. Following this,
continuous wear soft contact lens may be applied.
Advantage: good tensile strength
Drawback: it may form a solid, impermeable mass in situ and may
require removal.
153. Fibrin glue
Blood derived product that is
absorbable, easy to use and can be
kept at room temperature or
refrigerator.
Can be prepared at a blood bank, or
from patients own blood or
commercially available preparation.
Advantage: forms a smooth seal along
the perforation, less postop
discomfort.
154. Technique of Glue Application
Part preparation (paint and drapes), application of topical anesthetics and speculum
Debridement of necrotic tissue from ulcer crater
As tissue adhesive glue adheres best to basement membrane, 1-2 mm of normal epithelium should be
debride to allow the glue to properly adhere
Dry the site by methyl cellulose spear
As application in small amount to seal the perforation
Tissue adhesive solidify in few minutes via polymerization
Send this material for culture and sensitivity
A large heaped up mound is not required
155. Check the evidence Check for anterior chamber Apply bandage
of leakage by Seidel’s test maintenance (Air bubble contact lens
can also be used)
Tissue adhesive remains in place for weeks to
months until the perforation seals, it can be
removed or dislodges of its own
157. Surgical Management
a) If perforation is larger than 2mm (up to 4mm) corneal
patch graft can be applied.
b) If perforation is peripheral, tenoplasty may be done.
c) >4mm perforation, tectonic keratoplasty is required.
158. Therapeutic keratoplasty
Indications:
1. Conditions refractory to maximal
medical therapy
2. Carry a chance of scleral extension
3. Impending or already perforated ulcer
Goals:
1. Primary is to completely remove the
infective innoculum
2. Secondary is visual outcome
159. Therapeutic keratoplasty
Types
1. Lamellar thickness
2. Full thickness
Ideally fresh donor tissue is used, if not
available glycerine preserved corneal tissue
may be also used.
Gamma irradiated sterile corneas have longer
shelf life with low risk of infections.
Sometimes partial thickness scleral flaps
may be dissected with base at limbus,
reflected onto cornea and sutured for small
peripheral perforations, but these are
cosmetically less acceptable.
160. Lamellar keratoplasty
Advantages:
1. Because endothelium is not transplanted visually
devastating immune rejections are rare
2. Quality of donor endothelium is not a issue( deemed
unsuitable for pk)
Contraindications: deep stromal keratitis; impending
perforations
161. Amniotic membrane patch
graft
Amniotic membrane is folded in multiple
layers to fill the defect and then all layers
are sutured to the edges of corneal defect
with 10-0 monofilament suture.
It acts as a scaffold for epithelium to grow
and gets incorporated into the stroma.
Disadv: scar is dense and causes cosmetic
blemish.
162. Collagen cross-linking
Photoactivated corneal collagen cross
linking is developed recently to increase
the biomechanical strength of cornea.
In vitro studies have shown its beneficial
effect against few bacteria but not
successful against fungi, acanthamoeba.
Mechanism of action:
1. Interferes with enzymatic digestion
caused by PMNL
2. Antimicrobial effect –destroys microbial
cell wall through free radical production
163. Collagen cross-linking
Cornea contains riboflavin
but in a concentration
insufficient to have
antimicrobial effect.
In Cxl, epithelium
debridement is done,
cornea is soaked in
riboflavin solution and
then exposed to UV-A
irradiation.
By products of riboflavin (
oxygen and hydroxyl
radicals) damage the
nucleic acids of bacteria.
It has been a valuable
treatment option where
there is resistance to
antimicrobials; helps in
delaying keratoplasty.
164. MANAGEMENT OF CORNEAL SCAR
Attempted when cicatrization is complete & irritative signs
have passed.
Dense corneal scars in eyes with visual potential are treated
with corneal grafts
Lamellar keratoplasty may be advised for superficial scars.
When scar is full of thickness, penetrating full thicknning
keratoplasty is used.
In eyes with cornea with no visual potential, cosmetic contact
lens to hide the blemish.
Tattooing scars in otherwise blind eyes with Indian Ink or
impregnation with inks after stromal puncture are other
methods.
165. Flow Chart 2
Treatment Modalities
MEDICAL SURGICAL
1. Topical broad spectrum
preservative free eye drops.
2. Cycloplegics
3. Frequent lubrication with
preservative – free eye drops.
4. Oral and systemic antimicrobial
agents as per requirement.
5. Topical/systemic Steroids in
cases of PUK
1. Perforation less than 2mm: bandage
contact lens (BCL)
2. Size 2-3 mm: Application of tissues
adhesive with BCL
3. Size > 3 mm: Corneal patch graft /
multi-layered amniotic membrane
graft
4. Therapeutic penetrating
keratoplasty
5. Tarsorrhaphy: if lagophthalmos
present.
6. Punctal occlusion: if dry eyes is
associated.