SEA/Ophthal/126

Distribution : Limited

Guidelines
for the
Management
of
Corneal Ulcer
at
Primary, Secondary
& Tertiary Care health facilities
in the South-East Asia Region

World Health Organization

Regional Office for South-East Asia
2004
 Contents

1. Foreword
2. About the Publication
3. Guidelines for Management of
Suppurative Keratitis
Primary level
Secondary level
Tertiary level
4. Appendices
Epidemiology of Corneal Blindness
and Suppurative Keratitis in SEAR
Antimicrobial agents
References
Acknowledgements
Foreword

Launching of Vision 2020: The Right to Sight has given a new

impetus to the existing programmes for prevention of blindness
globally. Countries in the South-East Asia Region have been
quick to respond to this call.
While cataract remains the major cause of reversible visual
loss in the Region, diseases of the cornea are emerging as an
important cause of visual impairment. Trachoma and vitamin
A deficiency (xerophthalmia) have traditionally been the major
cause of corneal blindness. With the introduction of the SAFE
strategy for trachoma and mass distribution of vitamin A
capsules, both these conditions have now been brought under
control.
In the vast agrarian society of South-East Asia, particularly in
countries where primary health care and referral systems are
weak, minor eye injuries sustained in agricultural farms often
lead to corneal ulceration, loss of vision and many a time
result in loss of eyes. This is entirely avoidable if known public
health measures are applied effectively.
WHO together with its Member States is currently dealing
with this problem at two different levels. The first consists of
developing a community model for prevention of post-
traumatic corneal ulcer, and the second, providing a definitive
guideline for effective management of established corneal
ulcer.
The purpose of these guidelines is to provide a simple yet
effective management strategy to rapidly reduce morbidity
and visual loss due to corneal ulceration. I am confident that
this will be found useful by all those involved in caring for
these patients.
I would like to thank all our experts who have contributed to
the development of these guidelines.

Samlee Plianbangchang, M.D., Dr. P.H.

Regional Director
 About the Publication

Purpose
The purpose of this document is to provide guidance in the
management of superficial ocular trauma and established suppurative
keratitis in order to minimize morbidity and visual loss from bacterial
and fungal corneal infections.

Need and Process of Development of Guidelines

Corneal ulcer is a major public health problem in the (1-3, 5-18) developing
world causing prolonged morbidity, loss of vision and, many a time,
loss of eyes. It has tremendous socioeconomic implications as sufferers
are often the bread earners in the family.
Recognizing the public health importance of corneal ulcer, the WHO
South-East Asia Regional office has taken several initiatives in the
past, both for prevention of corneal ulcer as well as for its management,
in the countries of South-East Asia at the request of the governments.
Preventive interventions will be described in another publication. This
document describes the management of corneal ulcer.
Treatment of corneal ulcers has at best remained unsatisfactory across
the health systems of the developing world. The Regional Office
commissioned a study in 1999 to prepare an epidemiological and
microbiological profile of corneal ulcer in the Region. This study
identified the magnitude of the problem, microbial pattern of infection,
antibiotic/antifungal sensitivity of the microbes as well as modifiable
risk factors. This greatly helped to fill in the information gap.
Subsequently, these findings were reviewed at an intercountry meeting
on corneal blindness held in 2002. The participating countries
recommended to WHO to develop definitive guidelines for the
treatment of corneal ulcer suitable for use at different levels of health
system.
To respond to the above request, WHO entered into a contract with
the Aravind Eye Care System (AECS) in Madurai, India, a WHO
collaborating centre, for development of the guidelines. The first draft
of the guidelines was prepared by Dr M Srinivasan and his colleagues
based on the findings of the above cited study and review of the
more recent literature.
This draft was circulated among over 200 clinical and public health
experts. Their inputs were incorporated in the revised draft which
was reviewed by selected experts from six WHO collaborating centres
and corneal experts across the globe. The list of the collaborating
centres is given in Annex 6. The document was further refined at
Aravind Eye Care System and finally reviewed at WHO.
 1
Guidelines for the Management of
Superficial Corneal Trauma and Infections
in Primary Health Facilities

History and examination

If there is a:
• history of superficial injury; and/or
• examination shows a corneal abrasion

Treat
with chloramphenicol, eye ointment (0.5 - 1%)three times per day for at least 3
days.
7
• Do not use any medicine containing steroids.
• Do not use traditional medicines.

Refer to an ophthalmologist
• if pain and redness persist for 3 days; or
• if there is a white mark on the cornea and a red eye (corneal ulcer).
Give the patient chloramphenicol ointment to use 3 times per day when you
refer to an ophthalmologist or to the nearest eye care facility.
Do not delay the referral of a patient with corneal ulcer.

Clinical assessment and diagnosis

Primary level

Corneal abrasion Corneal ulcer

Inset abrasion without stain
8
2 9
Guidelines for the Management of
Suppurative Keratitis at the
Secondary Level of Eye Care

History and examination

Confirm diagnosis of suppurative keratitis (refer to Table 1 and photographs)

Immediate referral to a tertiary ophthalmic centre is

indicated if:
• the ulcer is in only eye
• the patient is a child
• there is impending or actual perforation
• a fungal ulcer is suspected on clinical examination, but KOH or other
fungal stain is not available.

Take a corneal smear:

and stain with KOH (or other fungal stain) (19-22) to look for fungal hyphae.

Admit the patient for in-patient treatment:

• if there is immediate threat to vision
• to ensure hourly treatment as below
• to ensure follow up as below
 Treatment guidelines

No fungal hyphae seen on smear Fungal hyphae seen on smear

Cafazolin 5% and Natamycin 5% drops hourly

Gentamycin 1.4% drops hourly alone (no antibiotics)

Ciprofloxacin may be used instead or Amphotericin 0.15% drops

of gentamycin. hourly
– if hourly drops is not possible
– then a sub-conjunctival inj.
can be considered.

Treatment frequency, duration and followup:

– Daily examination until the – Examination every 2 days
ulcer starts improving until the ulcer starts
improving

– Then gradually reduce the – Then continue drops at

10 frequency of drops and follow least 3 hourly for at
up over 2 weeks least 2 weeks after
healing of the ulcer

Refer to tertiary ophthalmic centre if:

Not improving after 3 days Not improving after 7 days
treatment treatment

Adjunctive therapy:
• Includes cycloplegics; analgesics; anti-glaucoma medication if
indicated.
• Do not use any preparation containing steroids.
• Investigate for diabetes mellitus as a possible risk factor for
corneal ulceration.
 Table-1: TTypical
ypical clinical features
Features of bacterial ulcer
1. History of trauma to the cornea,
contact lens wear
2. Pain, redness, watering,
decrease in vision
3. Lid oedema (marked in
gonococcal ulcer), purulent
discharge in gonococcal ulcer
and bluish green discharge in
pseudomonas corneal ulcer
4. Round or oval in shape involving
central or para central part of
the cornea.
Rest of the cornea is clear.
Hypopyon may or may not
be present.
5. In pneumococcal ulcer the
advancing border will have
active infiltrate with undermined
edges and the trailing
edge may show signs of healing.
Most of the pneumococcal ulcers
will show leveled hypopyon
associated with Dacryocystitis.
6. Pseudomonas ulcer will have
short duration, marked stromal
oedema adjacent to the ulcer
with rapid progression. If
untreated, will perforate within
2-3 days. Advanced ulcer may
involve the sclera also.
7. Ulcers caused by Moraxella and
Nocardia are slowly progressive
in immunocompromised hosts.
Features of fungal ulcer
1. History of trauma with
vegetable matter
2. Suspect fungal ulcer if
patient reports agriculture as
main occupation.
3. Pain and redness are similar
to bacterial ulcer. But lid
oedema is minimal even in
severe cases unless patients
have received native medicines
or peri ocular injections.
4. Early fungal ulcer may appear
like a dendritic ulcer of herpes
simplex virus. The feathery
11
borders are pathognomonic
clinical features. Satellite lesions,
immune ring, and unlevelled
hypopyon may aid in diagnosis.
5. The surface is raised with greyish
white creamy infiltrates, which
may or may not appear dry.
6. Ulcer due to pigmented fungi
will appear as brown or dark;
raised, dry, rough, leathery
plaque on the
surface of the cornea
 Early Bacterial ulcer

12
Late Bacterial ulcer

Early Fungal ulcer

Late Fungal ulcer

 Fig.1 Management of Supurative K eratitis at the
Keratitis
Secondar
Secondaryy LLevel
evel of eye care

Suppurative keratitis

Ulcer in an only eye

The patient is a child Yes Refer to Tertiary
Impending or actual perforation centre immediately
Suspected fungal ulcer

No

Perform KOH smear or other

fungal stain

13

Fungal hyphae seen

No Yes

Cefazolin 5% & Natamycin 5% or

Gentamycin 1.4% Amphotericin 0.15%
drops hourly drops hourly

Daily examination until Examination every 2 days

improvement until improvement

No
improvement
after 7 days

Refer to tertiary
ophthalmic centre
 How to per form a PPotassium
otassium hydroxide (K OH) & Lactophenol
(KOH)
cotton blue (LPCB) stain to identif y fungal hyphae

Equipment required Preparing 10% KOH smear

Essential equipment
Weigh approximately 10g
Kimura spatula
(8 pellets) of KOH
No 15 surgical blade Dissolve in 10ml of distilled
water
Sterile glass slides Add 1 drop of 10% glycerol
Cover slips Prepare fresh stock every
week
Binocular microscopes
Can be kept at room temperature
10% KOH in a dropper bottle
Spirit Lamp
Topical anaesthetic

Performing KOH smear Smear with fungal hyphae

1. Make the patient sit at the slit
lamp or lie down over a bed.
(need magnifiers, loupe or
operating microscope), explain
this simple procedure to
14 the patient
2. Instill one or two drops of
tetracaine or 0.5% proparacaine.
One can use 4% lignocaine if
the above two are not available.
Wait for a minute or two
before scraping.
3. Keep two clean glass slides
having 1cm circle made with
glass pencil on the reverse
side of the slide.
4. Scrape the base and edges of
the corneal ulcer with flame
sterilized kimura spatula or
sterile 15# Bard Parker blade.
5. Streak the specimen over the
glass slide within the circle;
one for KOH and the other
for Gram stain.
6. Apply KOH over the specimen.
Cover the KOH smear with a
cover slip and examine under
light microscope
immediately.
7. If the person is not trained to
interpret the smear, send both
slides immediately (within
2 hrs) to the microbiology
laboratory.
 Equipment required Preparing LPCB smear
Essential equipment Lacto phenol cotton blue can be
Kimura spatula obtained commercially and can be
stored for a indefinite period.
No 15 surgical blade
Sterile glass slides
Cover slips
Binocular microscopes
LPCB stain
Spirit Lamp
Topical anaesthetic

How to perform a LPCB smear Smear with fungal hyphae

1. Make the patient sit at the slit

lamp or lie down over a bed.
(need magnifiers, loupe or
15
operating microscope), explain
this simple procedure to
the patient
2. Instill one or two drops of
tetracaine or 0.5% proparacaine.
One can use 4% lignocaine if
the above two are not available.
Wait for a minute or two before
scraping.
3. Keep two clean glass slides
having 1cm circle made with
glass pencil on the reverse side
of the slide.
4. Scrape the base and edges of
the corneal ulcer with flame
sterilized kimura spatula or sterile
15# Bard Parker blade and
spread it on the glass slide
within the circle.
5. Apply locto phenol cotton blue
over the specimen.
6. Cover with a cover slip and
examine under light
microscope.
16
3
Guidelines for the Management of Suppurative
Keratitis at Tertiary Ophthalmic Centres

History and Examination:

Use a standard form and classification of corneal ulceration. (see Annex 4)

Take a Corneal Smear:

Stain with KOH (or other fungal stain) and Gram stain.

Culture on
(a) Sheep blood agar; (b) Sabourauds; and if possible
(c) Brain-heart infusion.
Other culture media may also be indicated in selected cases.

Admit the patient for in- patient treatment:

If there is immediate threat to vision
If the patient is a child 17
To ensure hourly treatment as below
To ensure follow -up as below

Treatment guidelines:
Smear No Gram Gram Fungal hyphae
not organism positive negative seen
possible seen on bacteria bacteria
smear seen seen
Cefazolin 5% and Natamycin 5%
Gentamycin 1.4% drops hourly drops hourly

Ciprofloxacin may be used instead or Amphotericin

of gentamycin. If hourly drops is not possible 0.15% drops
then a sub-conjunctival injection hourly
can be considered.

Treatment frequency, duration and follow-up:

Daily examination until the Examination every 2 days until
ulcer is improving the ulcer starts improving

Then gradually reduce frequency of Then continue drops at least 3

drops and follow up hourly for at least 2 weeks after
over 2 weeks healing of the ulcer
 Adjunctive therapy includes cycloplegics; analgesics; anti-glaucoma medication,
if indicated.
Figure 2 describes management if the ulcer does not respond to or worsens on
above treatment.

Fig.2: Decision making algorithm in the management of

therapeutic failures in presumed bacterial keratitis

Stop antibiotic for 24-48hr

No
Culture performed and reculture; conrneal biopsy in severe
progressive cases
Yes

Growth No Growth

Organisms No Change antibiotic to Add specific

susceptible cover organism media for bacteria,
to antibiotics used involved fungi and parasite
Yes
18

Wait for Consider

72 hours of No Growth of No Surgical
72 hrs of
therapy organism Options
treatment

Yes
Yes

Treat
specifically

Host
Inadequate dosing Non-compliance
immunocompromised

Increase to hourly Repeat subconj. Supplement drops

dosing Injection and or with subconj.inj
hospitalize & consider systemic
antibiotics treat
the cause
Role of Topical Steroids
Topical steroids are not recommended in any case of fungal keratitis.
The role of topical steroids in bacterial keratitis is controversial.
If steroids are used it should be with great caution and close obser
vation.

Role of Systemic Antimicrobials

Systemic antifungals are recommended in fungal ulcers, which are:
large and deep, or
perforating, or
have scleral involvement
Systemic antibiotics are recommended in bacterial ulcers if there is scleral
involvement and may be used in perforated cases.

Role of Surgery
Surgical procedures may include:

Debridement/superficial keratectomy
Surgical removal of corneal epithelium without causing injury to the basement
membrane.
19
Indication
Epithelial herpes simplex virus keratitis
Recurrent corneal erosion
For diagnosing superficial infective keratitis
Enhances penetration of topical antibiotics.

Techniques
This procedure is performed under topical anaesthesia on a slit lamp or operating
microscope with sterile cotton tipped applicator, weckel sponge or surgical blade.

Superficial Keratectomy
Surgical removal of corneal epithelium including Bowman’s membrane and
anterior stroma of the diseased cornea.

Indication
Biopsy in non-healing corneal ulcer
Debulking of infective material

Technique
This procedure is performed under aseptic condition with topical or
subconjunctival anaesthesia using 15# Bard Parker blade.
 Tarsorrhaphy
Lateral
Central

Indication
Exposure keratitis (Bells palsy)
Neuroparalytic keratitis
Lateral tarsorraphy is frequently performed in an eye having Bell’s palsy with
non-healing suppurative keratitis.

Technique
This procedure is performed at a minor operating theatre: Local infiltration with
2% lidocaine at the lid margins. About 1-2 mm of inter-marginal strip is shaved
off deep upto dermis and apposed with 4 “0” silk suture and anchored with
bolsters. The release of tarsorraphy depends upon the etiology of lagophthalmus
and healing response of the ulcer.

Tissue Adhesive
This procedure is performed for:
wounds with a small amount of tissue loss
persistent aqueous leakage
small lacerations
20 puncture wounds
The tissue bed must be dry and free of epithelial cells.

Technique
A thin film of adhesive is applied using a small gauge disposable needle, a
micro capillary applicator or the broken wooden end of a sterile cotton applicator.
Following application, adhesives should be given several minutes to dry before
any other manipulation.

Conjunctival flaps
This is rarely performed for suppurative keratitis.

Indications
Non-healing superficial ulcer
Peripheral corneal ulcers with descemetole or small perforation

Contraindication
Perforated central corneal ulcer

Advantages
Promotes healing providing better nourishment to the underlying cornea

Disadvantages
Monitoring the progress of ulcer is difficult
Delays or impedes the penetration of topical antibiotics
Visual outcome will be poor due to scarring and vascularisation
 Technique
This procedure is performed under local anaesthesia as in cataract surgery. It is
taken up under general anaesthesia if the patient is non-cooperative or in the
paediatric age group. Specific drugs should be continued post-operatively.

Patch Graft
Indication
Descemetocele
Small perforation
Patchgraft is usually 5 mm or 6 mm in size. Recipient bed is cleared of debris
and not trephined. Lamellar or full thickness donor button could be anchored.
This procedure is performed in the operating room under surgical microscope.
Interrupted suture (12-16) is applied using 10/o or 9/o nylon. Appropriate
antibiotics are continued post-operatively.

Penetrating keratoplasty
Maintains the integrity of the globe for future optical grafts
Promotes healing of corneal ulcer by total removal of pathology
As a diagnostic technique to form a good source for histopathologi
cal and microbiological examination
40-50% of these patients recover useful vision
Carries better prognosis in bacterial corneal ulcers
21
The indications for surgical intervention include:
Non-healing in spite of all medical therapy
Impending or actual perforation

If the ulcer does not respond to treatment:

Review with gram stain, culture and sensitivity results
If the organism is unknown, consider stopping all treatment for 48
hours, take new smears, cultures, and if required a corneal biopsy.
Use culture media for viral and uncommon pathogens. (anaerobes,
acanthamoeba, mycobacteria).
 References

1. Katz NNK, Wadud SA, Ayazuddin M. Corneal ulcer in Bangladesh. Annals

of Ophthalmology 1983; 15 : 834-836
2. Bharathi MJ, Ramakrishnan R, Vasu S. Epidemiology of bacterial keratitis
in a referral centre in south India. Indian J Ophthalmol (in press)
3. Goonawardana SA, Ranasinghe KP, Arseculeretnae SN, et al. Survey of
mycotic and bacterial keratitis in Sri Lanka. Mycopathologia 1994; 127:
77-81
4. Ginrich WD. Keratomycosis. JAMA 1962: 179: 602 - 8.
5. Srinivasan M, Gonzales CA, George C, et al. Epidemiology and
aetiological diagnosis of corneal ulceration in Madurai, south India. Br J
Ophthalmol 1997; 81: 965-971
6. Bharathi MJ,Ramakrishnan R, Vasu S. Nocardia asteroides keratitis in
South India.Indian J Med Microbiology 2003;21 31 - 36
7. Mahajan VM. Ulcerative keratitis: an analysis of laboratory data in 674
cases. J Ocul Ther Surg 1985; 4: 138-41
8. Kotigadde S, Ballal M, Jyotirlatha, et al. Mycotic keratitis: a study in
coastal Karnataka. Indian J Ophthalmol 1992; 40: 31-3
9. Sundaram BM, Badrinath SS, Subramaniam S. Studies on mycotic
22
keratitis. Mycoses 1989; 32: 568-72
10. Venugopal PL, Venugopal TL, Gomathi A, et al. Mycotic Keratitis in
Madras. Indian J Pathol Microbiol 1989; 32: 190-7
11. Imwidthaya P.Mycotic keratits in Thailand. J Med Vet Mycol 1995; 33:
81-2
12. Thomas PH. Mycotic keratitis - underestimate of mycoses. J Med Vet
Mycol 1994;32:235-56.
13. Bharathi MJ, Ramakrishnan R, Vasu S, et al. Aetiological diagnosis of
Microbial keratitis in south India. Indian J Med Microbiol 2002; 20: 19-
24.
14. Sharma S, Sujatha G, Murali AK, Garg P, Rao GN Trends in contact lens
associated microbial keratitis in southern India. Ophthalmology, 2003;
110: 138 - 143.
15. Garg P, Sharma S, Rao G Net al. Ciprofloxacin resistant pseudomonas
keratitis. Ophthalmology 1999; 106: 1319
16. The Central Microbial Keratitis: The Philippine Journal of
Ophthalmology.vol 25 No.1 supplement; January - March 2000, 23-31
17. Gopinathan U, Garg P, Fernandes M, Sharma S, et al. The Epidemiological
features and laboratory results of Fungal Keratitis. Cornea, 2002; 21 555
- 559.
18. Parmar P, Salman A, Kalavalhy M et al. Pneumococcal keratitis - a clinical
profile: Clinical and Experimental ophthalmology 2003; 31:44-47.
19. Bharathi MJ, Ramakrishnan R, Vasu S, et al. Epidemiological characteristics
and laboratory diagnosis of fungal keratitis: a three year study. Indian J
Ophthalmol 2003: 51 : 315 - 321
20. Medical Laboratory Manual for Tropical countries; Vol II Microbiology,
Monica Cheesbrough, Tropical Health Technology/Butteys worth
21. Gorner JT, Robinson NM, Osato M, Wilhelmus KR. Comparison of acridine
orange and Gram stains in bacterial keratitis. A J. Ophthalmol 1998; 106:
735-37.
22. Groden LR, Rodenite J, Brinson JH, Gewvert GI. Acridine orange and
Gram stains in infectious keratitis. Cornea 1990; 9:1222-24.
23. Jones DB. Decision making in the management of microbial keratitis.
Ophthalmol 1981; 88: 814-20.
24. Wahl JC, Katz HR, Abrams DA. Infectious keratitis in Baltimore. Ann
Ophthalmol 1991;23:234-7.
25. Harris DJ Stulting RD,Waring GO, Late bacterial and fungal keratitis after
corneal transplantation; spectrum of pathogoneris, graft survival and visual
progress Ophthalmology 1988,95: 1450 - 7
26. Liesegang TJ, Forster RK. Spectrum of microbial keratitis in South Florida.
Am J Ophthalmol, 1980 90:38-41.
27. Forster R, Resell G. The diagnosis and management of keratomycosis -
Cause and diagnosis. Arch Ophthalmol, 1975; 93:975-8. 23
28. Vajpayee RB, Dada T, Saxena R, et al. Study of first contact management
profile of cases of infectious keratitis- A hospital based study. Cornea,
2000; 19:52-56
29. Mcleod S, Kolahdouz, khodam I, et al. Role of smears, cultures and
antibiotic testing with management of suspected infectious keratitis.
Ophthalmology 1996; 103: 23 - 28
30. Dart JKG, Stapleto NF, Minassian D. Contact lenses and other risk factors
in microbial keratitis. Lancet 1991; 338:650-3
31. Ormerod FD, Hertzmark E, Gomez DS et al. Epidemiology of microbial
keratitis in southern California. Ophthalmology 1987; 94:1322-33.
32. Boonpasart S, Kasetsuwan N, Puangsricharern V. Infectious keratitis at
King Chulalongkorn Memorial Hospital: a 12 year retrospective study of
391 cases. J Med Assoc Thai 2002; 85( suppl 1): S217-30
33. Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global
perspective Bull WHO 2001; 79: 214-221
34. Upadhyay MP, Karmacharya PC, Koirala S, et al. Epidemiologic
characteristics, predisposing factors, and aetiological diagnosis of corneal
ulceration in Nepal. Am J Ophthalmol 1991; 111: 92-9
35. Upadhyay MP, Rai NC, Brandt F, Shrestha RB. Corneal ulcers in Nepal.
Graefe’s Arch Clin Exp Ophthlamol 1982; 219: 55-9
36. Wong TY, Fong KS, Tan DT. Clinical and microbiological spectrum of
fungal keratitis in Singapore: a five year retrospective study. Int Ophthalmol
1997; 21: 127-30
 37. Houang E, Lam D, Fan D, Seal D. Microbial keratitis in Hong Kong:
relationship to climate, environment and contact lens disinfection. Trans
R Soc Trop Med Hyg 2001; 95: 361-7
38. Upadhyay MP, Karmacharya PC, Koirala S, et al. The Bhaktapur Eye Study:
Ocular trauma and antibiotic prophylaxis for the prevention of corneal
ulceration in Nepal. Br J Ophthalmol 2001; 85: 388-92
39. Rahman MR, Johnson GJ, Husain R, et al. Randomised trial of 0.2%
chlorhexidine gluconate and 2.5% natamycin for fungal keratitis in
Bangladesh. Br J Ophthalmol 1998; 82: 919-25
40. Dunlop AA, Wright ED, Howlander SA, et al. Suppurative corneal
ulceration in Bangladesh. A study of 142 cases examining the
microbiological diagnosis, clinical and epidemiological features of bacterial
and fungal keratitis. Aust N Z Ophthalmol 1994; 22: 105-10
41. Williams G, McClellan K, Billson F. Suppurative keratitis in rural
Bangladesh: the value of gram staining in planning management. Int
Ophthalmol 1991; 15(2): 131-5
42. Williams G, Billson F, Husain R, et al. Microbiological diagnosis of
suppurative keratitis in Bangladesh. Br J Ophthalmol 1987; 71: 315-21
43. Leck AK, Thomas PA, Hagan M, et al. Aetiology of suppurative corneal
ulcers in Ghana and south India, and epidemiology of fungal keratitis. Br
24 J Ophthalmol 2002; 86: 1211-15
44. Mah FS New antibiotics for bacterial infections. Ophthalmol Clin N Am
2003; 16: 11-27
45. Gangopadhyay N, Daniell M, Weih L, Taylor HR. Fluoroquinolone and
fortified antibiotics for treating bacterial corneal ulcers. Br J Ophthalmol
2000; 84: 378-84
46. Kowalski RP, Karenchak LM, Romanowski EG. Infectious disease: changing
antibiotic susceptibility. Ophthalmol Clin N Am. 2003; 16:1-9
47. Bharathi MJ, Ramakrishnan R, Vasu S, et al. In vitro efficacy of antibacterials
against bacterial isolates from corneal ulcers. Indian J Opthalmol 2002;
50: 109-114
Dandona R and Dandona L “Current Ophthalmology:Review of findings
of the APEDS - Andhrapradesh Eye Disease Study:1. policy implications
for eye care services. Int J. Ophthalmol; 2001; 49: 215-234
 Annex-1

Epidemiology & Management Corneal Blindness and

Suppurative Keratitis

1. Epidemiology of Corneal Visual Loss

(a) The magnitude of blindness (all causes) in the countries of the South-East
Asia Region varies from 3 000 people per million population in
communities with good economy and health care to over 10 000 per
million in low-income settings.
(b) Corneal scarring is a common cause of blindness in low-income settings
being responsible for 5-20% of all blindness.
(c) Important causes of bilateral corneal blindness include trachoma, vitamin
A deficiency, ophthalmia neonatorum and bacterial/fungal infections.
(d) The Andhra Pradesh Eye Disease Study (APEDS) (48) in Andhra Pradesh
(India) estimated that 1,200 people per million population are blind (<3/
60) from corneal pathology.
(e) The prevalence of unilateral blindness due to corneal opacity in low-
income settings is estimated to be in the range of 5,000 to 20,000 people
25
per million population.

2. Epidemiology of Suppurative Keratitis

(a) Suppurative keratitis due to bacteria and fungi is the main cause of
unilateral corneal scar.
(b) A two-year prospective study of over 34 000 people from a rural setting
in Nepal reported an incidence rate of corneal ulceration of 8000 cases
per million population per year (160 cases per million pop per week).
The results of retrospective studies in the Region are summarized in Table
1. It is estimated that up to 12 million cases of suppurative keratitis occur
each year in the Region. An unknown proportion of these cases go on to
visual loss or blindness.
(c) Within the SEA Region the causes of suppurative keratitis depend mainly
on climatic factors.
(d) In warm, humid areas the relative proportion of fungal to bacterial ulcers
approaches 50:50, while in cool dry climates most ulcers are due to
bacteria.
(e) The major bacterial causes are streptococcus; pseudomonas and
staphylococcus.
(f) The major fungal isolates are fusarium and aspergillus species. Candida is
relatively uncommon.
(g) Acanthamoeba even in well-equipped tertiary facilities is responsible for
less than 5% of ulcers.
 (h) Agricultural trauma is the main risk factor; seasonal variations in incidence
can occur. Contact lens wear is not an important risk factor within the
Region.

3. Management of Suppurative Keratitis

(a) The outcome of corneal injury with secondary infection can be markedly
improved by early diagnosis and appropriate treatment with antibiotics at
the primary level of health care.
(b) Inappropriate use of traditional medicines or topical steroids and delay in
referral to an ophthalmologist for diagnosis and treatment all contribute
to unnecessary visual loss from superficial corneal trauma and secondary
infection.
(c) Identification of fungal hyphae in a corneal smear with KOH stain is a
simple, inexpensive and sensitive test, which should routinely be
performed by ophthalmologists in cases of suppurative keratitis, particularly
in areas where fungi are known or expected to occur.
Lactophenol cotton blue is a simple alternative fungal stain reported from
some countries.
(d) Antifungal treatment is not recommended unless there is evidence of
fungal infection by microscopy or culture. Natamycin is the drug of first
26 choice in geographical areas where fusarium species predominate.
(e) The recommended first line antibiotic treatment is a combination of
cephazolin and fortified gentamycin.
 Table 1: R epor ted incidence of corneal
eported
ulceration in the SEA Region*
Country Incidence / Reference Comment
(million pop)

Nepal 7990 BJO 41 Prospective 2 yr study

India 1130 BJO 5 Retrospective study
Myanmar 7100 *Country report Retrospective study
Bhutan 3390 *Country report Retrospective study

Table 2: PPropor
roportion of suppurative keratitis with
roportion
fungal organisms in the SEA Region*

Organism Sri Lanka India Nepal Bangladesh Thailand

Any fungus 33 19-45 17-44 21-36 25

Table 3: Microbiological profile of fungal Keratitis

Keratitis
in the SEA Region*
(Percentages) 27
Organism Sri Lanka India Nepal Bangladesh Thailand

Aspergillus 18 16-53 46-60 29-29 34

Fusarium 80 10-47 13 14-28 26

Table 4: Microbiological profile of bacterial keratitis

in the SEA Region*39 - 45
(Percentages)
Organism India Nepal Bangladesh Thailand
Steptococcus pneumoniae 44 31 22 3
Pseudomonas aeruginosa 10 12 11 7
Staphylococcus epidermidis 14 11 20 45
Others or unknown bacteria 32 46 47 45

* (Figures as repor ted by Member Countries based on their hospital data projected to
a captive population)
 Annex 2

Antimicrobial agents

Sensitive Common
Antibiotic organisms Dose Comment
resistance

Cefazolin Strep pneumo, Most gram – 5.0% Not

and most bacteria commercially
gram+ bact. available,
must be prep-
ared from
injectable
form as and
when necessary

Gentamycin Most gram – Strep 1.4% Commercial

and some pneumo drops need
gram + bact. to be fortified

Ciproflox- Most gram – Most Strep 0.3% Commercially

acin and many pneumo available
28
gram + bact.

Chloram- Many gram Good for 1.0% Commercially

phenicol + and pneumo available in
gram – bact. drops and
ointment

Antifungual

Natamycin Filamentous --------- 5.0% Commercial

fungi – ------ available
Fusarium

Amphote- Effective Moderate 0.15% Not commer-

ricin – B against most response to cially available,
yeasts Fusarium must be prep-
Aspergillus ared from an
injectable
preparation
 Annex 3

Classification, Dosage and

Spectrum of useful Antifungal agents

Dosage

Drug Topical Systemic Useful

antifungal
spectrum

Polyene 3.3% ointment Poorly soluble, Moderately

Antifungals or 100 000 not absorbable effective against
Tetrenes units/g every hr from most Candida
during day, gastrointestinal species. Slight
every 2hr at tract. Not effect against
Nystatin night recommended filamentous
for systemic use fungi.

Natamycin 5% suspension Poorly soluble, Good effect

every hr during not against Candida,
day, every 2hr recommended Aspergillus, 29
during night for systemic Fusarium and
use some other
fungi. Poorly
soluble, difficult
to treat deep
mycotic corneal
ucler

Pentenes 0.5% solution 0.25mg/kg on Highly effective

too toxic; 0.1 day 1; increase against Candida,
to 0.2% by 0.25 to moderately
Amphotericin– solution 1mg/kg/day. effective
B effective every Total dosage against some
hr during day 1000-1500mg. filamentous
every 2hr at Use 50 mg fungi.
night diphenhydra- Excellent for
mine systemic use
orally before against Candida.
dose. Give as Synergistic with
intravenous drip flucytosine and
in 5% dextrose this combination
and water with is
1000 units recommended
heparin
 Dosage

Drug Topical Systemic Useful

antifungal
spectrum

Imidozole 1% solution in 60mg-100mg/ Highly effective

derivative arachis oil kg/day for against Aspergi-
antifungals every 1hr until 2 weeks llus Candida
Trityl response species, and
imidozole occurs, then 4 some filamentous
group times a day for fungi, including
8 to 12 Paecilomyces,
Clotrimazole weeks Dreschlera,
Alternaria, &
Cladosporium
species. Poor
effect against
Fusarium.

Phenethylalco 1% solution in 300 to 600 mg/ Active against a

hol group arachis oil day larger spectrum
Miconazole every 1 hr intravenously of filamentous
30
during day, has been used fungi and
every 2hr at for ocular Candida
night infection organisms, but
less effective
against
Aspergillus and
Fusarium species
than other
agents. It also
has some anti-
bacterial
activity against
gram positive
organisms

Econazole 1% solution in 200mg/day More effective

arachis oil systemically than Miconzole
every hr during against
day, every 2hr Aspergillus,
during night Fusarium,
and Pencillium
species but less
effective against
Candida species
 Dosage

Drug Topical Systemic Useful

antifungal
spectrum

Itraconazole 1% suspension Oral adult dose It has a wider

and 1% 200mg/day. It spectrum of
ointment should be activity than
continued for Imidozoles. It
1-2 moths has an excellent
in vitro activity
against
Aspergillus and
Candida. It has
not been very
effective against
Fusarium. Oral
administration of
Itracanozole
appears to have
less penetration
than other
triazoles into the 31
cornea, aqueous
and vitreous.

Pyramidime 1% solution for 150 mg/g/day Effective against

5-Flurocytisine topical use is by oral route. Candida,
well Can also be Cryptococosis
tolerated administered and related fungi.
intravenously Resistant
strains emerge
rapidly on
monotherpy,
usually
combined with
Amphotericin-B
for treatment of
sensitive fungi.

Adapted in part from Jones BR : principles in the management of Oculomycosis. Am J

Ophthalmol, 1975; 79 : 719 and Thomas P A: Fungal infections of the corneal Eye 2003,
17:852-862.
 Annex 4

Standard Clinical Examination Form for Tertiary

Care Center: Corneal Ulcer Patient Proforma
Patient details Patient number:
Name: Age: ______ Sex: M F
Address : ________________________________

Ophthalmic history
Trauma Eye surgery
Dacrocystitis Ocular surface disorder
Corneal exposure Trichiasis
Contact lens wear Diabetes mellitus

Does the patient have a history of diabetes? Y/N.

32 If yes, for how long _________

If other, give details:

Current topical antibiotic Y / N specify ______________

Current topical antifungal Y / N specify ______________

Current topical steroid Y/N specify ______________

Traditional eye medicine Y / N specify ______________

Presentation Date of primary presentation ___/____/____

Eye RE / LE / Bilateral

Duration of symptoms _______ days

Visual Acuity (uncorrected) Right ________ Left ________

BASE - LINE EXAMINATION

Ulcer size
 Lid Oedema
Mild Moderate Severe

Depth of Ulcer
Deep Superficial

Depth of infiltrate
Anterior stroma Mid stroma Posterior stroma

Hypopyon
Absent Present
Height __________mm
REVIEW Date: _____/____/____

MICROBIOLOGY RESULTS
Gram stain ____________________ date ___/___/___
KOH ____________________ date ___/___/___
Locto phenol
Cotton Blue ____________________ date ___/___/___ 33
Culture (BA) ____________________ date ___/___/___
Culture (SDA) ____________________ date ___/___/___
others (specify) date ___/___/___

Eye RE / LE / Bilateral
Visual Acuity Right __________ Left _________

Ulcer size :

Depth of infiltrate Anterior stroma

Mid stroma Posterior stroma

Hypopyon
Absent Present
Height __________mm
Assessment
Healing No Change
Working Perforation
 Annex 5

Classification of Corneal Ulcers

Microbial ulcers
These are caused by Staph or Strep species, present with pain, redness, lid
oedema and discharge that varies according to the duration and severity of the
ulcer. The ulcer is well circumscribed and may be central or at mid-periphery of
the cornea. The borders of the ulcer are usually round or oval. Stromal infiltration
may be present under the base of the ulcer with a yellowish white appearance.
In severe ulcers, there may be folds in the deep stroma radiating from the ulcer
bed; additionally a levelled hypopyon, 3 to 4 + cells and flare may be seen.
Rarely posterior corneal abscess may be present with intact epithelium.

Pneumococcal ulcer:
May be associated with chronic dacryocystitis in 55% of cases 2, 18.
Haemorrhagic hypopyon may be associated with pneumococcal ulcer.
Frequently seen in corneas having degeneration, epithelial problem and
scars.
The creeping edges and dense infiltrate at the leading edge of the ulcer
are characteristic clinical features of pneumococcal ulcer.
34
Gram positive bacterial ulcers
The uninvolved portion of cornea will appear clear without oedema or infiltration.

Gram negative bacterial ulcer

Pseudomonas ulcer will have a short history.
Signs and symptoms will be severe
Diffuse ulceration with stromal infiltrate or oedema involving adjacent or
whole cornea resulting in ground glass appearance is a distinguishing
clinical feature from other ulcers. Mucopurulent discharge is seen
frequently and it appears bluish green in untreated severe pseudomonas
ulcers.
Marked lid oedema and chemosis than seen in Gram positive bacterial
ulcers.
The ulcer perforates within few days if not managed properly.
Pseudomonas ulcer may develop as ring abscess without epithelial defect.

Ulcer caused by gram negative cocci

Marked lid oedema and copious purulent discharge;
Pus will spurt out when the lids are separated.
Ulcer is usually bilateral and perforates within short duration.
Lid abnormalities like ectropion, entropion, trichiasis, improper closure of lids
as in leprosy, neurotrophic lesions due to herpes simplex, zoster or corneal
degenerations, bullous keratopathy, and dry eyes predispose to bacterial ulcer
in the SEA Region.
Satellite lesions, immune ring, endothelial plaques are present in both
bacterial and fungal keratitis and do not help to differentiate between
bacterial and fungal keratitis.
Fungal Keratitis
The ulcer usually involves the central or exposed part of cornea.
The edges are feathery with finger like projections, mimicking a herpetic
dendritic ulcer in early stages.
The fungal ulcer has raised creamy surface with greyish white infiltrate;
The base of the ulcer is dry leathery (not in early fungal ulcer of about
one week duration).
The hypopyon is unlevelled and solid.
There may be posterior corneal abscess with intact corneal epithelium.
The remaining cornea appears clear.

Pigmented fungal ulcer

The surface will show brown or dark pigmentation which is tough and
leathery;
Very difficult to scrape for diagnostic or therapeutic purposes.
Untreated or improperly treated ulcer may progress to involve sclera also.

Fungal ulcer caused by Candida

Usually involves an immunocompromised host and cornea; 35
The ulcer appears as collar button and mimics staphylococcal ulcer.
 Annex 6

List of WHO Collaborating Centres participating

in the development of the Guidelines
1. Aravind Eye Hospitals and Aravind Eye Care System, Madurai, India
2. L V Prasad Eye Institute, Hyderabad, India
3. Dr R P Centre for Ophthalmic Sciences, New Delhi, India
4. London School of Hygine and Tropical Medicine London, UK
5. Proctor Foundation for Research in Vision and Ophthalmology University
of California, San Fransisco, USA
6. Department of Ophthalmology, Juntendo University, Tokyo, Japan.

36
Acknowledgements

We would like to thank Dr M. Srinivasan, Director of the Cornea Service of

Aravind Eye Care System (AES), Madurai, India for undertaking to review the
available literature on corneal ulcer and for preparing the Guidelines
incorporating changes at different levels. We would also like to thank the
ophthalmologists and public health experts who gave us their comments on
the first draft. We would like to gratefully acknowledge the help of the following
experts who participated in a workshop to finalize the draft: Prof Allen Foster,
London School of Hygiene and Tropical Medicine, U.K; Dr Prashanth Garg,
L.V.Prasad Eye Institute, Hyderabad, India; Dr Steven McLeod, Proctor
Foundation, University of California, San Francisco, USA, Dr John P. Whitcher,
Proctor Foundation University of California San Francisco,USA; Dr Sanduk
Ruit, Tilganga Eye Center, Kathmandu, Nepal; Prof. K Konyama, Juntendo
University, Tokyo, Japan, Dr J.S.Titiyal, R.P.Centre, All India Institute of Medical
Sciences,New Delhi,India and Dr Md.Saleh Ahmed, National Institute of
Ophthalmology, Dhaka, Bangladesh.
Dr R. Pararajasegaram and Dr Madan P Upadhyay also participated at the
expert group meeting on behalf of WHO.