International Journal of Health Sciences and Research

Vol.10; Issue: 3; March 2020

Website: www.ijhsr.org
Review Article ISSN: 2249-9571

Diagnosis and Management Protocol of Acute

Corneal Ulcer
Vaishal P Kenia1, Raj V Kenia2, Onkar H Pirdankar3
1
Kenia Eye Hospital, Mumbai
2
Kenia Foundation, Mumbai
3
Kenia Medical and Research Foundation, Mumbai
Corresponding Author: Onkar H Pirdankar

ABSTRACT

Corneal ulceration is one of the leading causes of corneal blindness. Various pathogens are
responsible for corneal ulceration. Accurate and quick diagnosis and prompt treatment is a key to
improve clinical and visual outcomes in cases of corneal ulceration. However there are no specific
guidelines or protocols are available for managing the corneal ulcers. Sometimes even an experienced
clinician struggle to predict the course of the disease in most of the cases. Here we make an attempt to
provide an overview on diagnostic approach and management protocol of acute corneal ulcer.

Key words: Acute corneal ulcer, corneal ulceration, corneal blindness

INTRODUCTION parasitic (Acanthamoeba).Whereas the non-

Corneal ulceration is one of the infectious causes are autoimmune,
major ocular emergencies causing ocular neurotrophic, toxic, allergic keratitis,
morbidity. It is considered a leading cause chemical burns, keratitis secondary to
of corneal blindness especially in the entropion, trichiasis, blepharitis,
developing countries. It has been estimated lagophthalmos.
that globally, corneal ulceration with ocular Infectious causes of corneal
trauma are resulting in 1.5 -2 million cases ulceration vary based on geographic
of corneal blindness annually 1. It affects location. The common microorganism are
males more than the females, can be seen at Fusarium species, Pseudomonas aeruginosa,
any age and mostly the patients belong to a Aspergillus spp., S. Pneumoniae,
low socio-economic strata 2,3. In developing Staphylococcus Spp. Fungal organisms are
countries like India, the major reason for common in Countries like India, China. In
corneal ulcer is ocular trauma whereas in other countries such as Philippines, Taiwan,
the developed countries, the most common Thailand and Singapore bacterial organisms
reason is contact lens wear. such as Pseudomonas aeruginosa is
Etiology and Epidemiology: common. Table 1 describes the common
The causes of a corneal ulcer can be microorganisms, by counties 4.
infections like bacteria, viruses, fungi or

Common organism Total IND CH SG PH JP TH KR TW

Bacterial 38.0% 38.3% 15.3% 41.3% 53.2% 47.8% 50.5% 42.8% 61.8%
Fungal 32.7 45.6% 30.2% 0.7% 27.0% 6.3% 9.1% 10.0% 8.2%
Parasitic 2.4 2.1% 0.9% 1.3% 5.7% 5.0% 4.0% 1.2% 6.9%
Viral 12.6% 6.9% 46.2% 7.0% 2.0% 16.6% 6.1% 6.0% 8.2%
Infectious 14.5% 7.1% 4.4% 49.7% 12.1% 24.3% 30.3% 40.0% 15.0%
Keratitis (Not Specified)

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Vol.10; Issue: 3; March 2020
 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Table 1 describes common organism found response is less aggressive and slow
in Asian countries (IND-India, Ch- China, compared to bacteria. Fungus secretes
SG- Singapore, PH- Philippines, JP- Japan, proteolytic enzymes and fungal antigens and
TH-Thailand, KR- South Korea, TW- toxins which facilitates their deeper stromal
Taiwan) penetration and breach the descemets
membrane and thereby reach anterior
Pathogenesis: chamber where it forms fungus-exudate-iris
Bacterial: mass covering the pupillary area. 5
Bacterial corneal ulcers are results Viral:
from the penetration of bacteria after a In viral ulcer, the virus reaches the cornea
breach in the corneal epithelial barrier from within via terminal branches of
except organisms like gonococcus can ophthalmic division of the trigeminal nerve.
penetrate an intact epithelium to cause ulcer. It has been postulated that in case of herpes
Factors predisposing the epithelium like simplex there is an involvement of the sub
corneal edema, prolonged contact lens basal nerves which results in epithelial
usage, dry eyes, and trauma make it swelling whereas in case of herpes zoster
vulnerable to corneal infection. The most there is an involvement of deep stromal
common microorganism is Pseudomonas nerves. So without epithelial breach the
Aeruginosa which utilizes glycocaluxto virus reaches the eye via nerve endings and
adhere to epithelium and then invades into the inflammation of nerve causes
the stroma through breach in epithelial. neurogenic pain. The virus actively
Inflammatory cells (PMNs) reach the site of replicates in corneal epithelium. The virus
corneal breach from the tears and limbal in the epithelium form raised lesion forming
vessels which releases cytokines and superficial punctate keratitis and then
interleukins resulting in progressive slough to form large epithelial defect and
invasion of cornea and increase in size of eventually stromal ulceration.
the ulcer. Phagocytosis of the organism Parasites such as acanthamoeba:
releases the free radicals and proteolytic Acanthamoeba keratitis is most commonly
enzymes leading to necrosis and sloughing associated with soft contact lens use, Once it
of the epithelium, bowman’s membrane and is adherent to the contact lens, it survives in
stroma. In addition, process is facilitated by the space between the contact lens and the
proteases and exotoxin that are produced by ocular surface and later gets attached to the
multiplying bacteria and endotoxin that are glycoproteins on the corneal villi. The
produced by organisms after their death. microtrauma to the corneal epithelial
The endotoxins are polysaccharides within surface due to contact lens use promotes the
the cell wall of gram negative bacteria and entry of the organism into the epithelium,
are responsible for ring infiltrates. 3,4 the invade Bowman's layer and enter the
Fungal: stroma. The infection then moves along the
Fungus are classified as yeast, filamentous corneal nerves, produces acute
septated, pigmented and non-pigmented and inflammation and radial deposits (radial
filamentous without septae. In the tropical keratoneuritis). The acute inflammation
countries, the commonest fungus is produces metalloproteases that digests
filamentous like Aspergillus, Fusarium, in collagen fibrils and allows deeper
temperate countries yeast fungus like penetration into the stroma. As the disease
candida is common. Fungal pathogens also progresses, it may penetrate the anterior
enter the cornea after an epithelial breach, chamber and can cause endophthalmitis.
following trauma or foreign body in the Symptoms: 6,7
form of vegetative material or soil particles  Reduced visual acuity,
and after invasion incite a host  Tearing,
inflammatory response. The inflammatory  Discharge,

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 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

 Redness are the common symptoms long-term use of ocular medications (topical
presented by the patients. steroids, Anti-glaucoma medications),
 Pain (Disproportionate pain can be seen contact lens wear (age of contact lens and
in Herpes and Acanthamoeba. Fungal lens cleaning solution), and previous ocular
ulcers are quieter whereas pseudomonas infections is important as all these factors
are fast growing) alter the ocular surface milieu and promote
 Diagnostic Approach: microbial invasion of the cornea in the
absence of trauma. Similarly, systemic
Careful History: diseases such as diabetes, rheumatoid
It is very important to keep in mind arthritis, hepatitis, auto-immune diseases
the TRIAD of ocular trauma, Lowered and their therapy, tuberculosis, malignancy
immune status (either the ocular surface or impair the natural immune status of an
the individual as a whole) or extremely individual and predisposes to opportunistic
virulent organisms that penetrate the intact infections, unusual microbes, fungi or
ocular surface. A corneal ulcer cannot viruses.
develop in a healthy individual with a Thorough Slit lamp Biomicroscopy:
healthy ocular surface, in the absence of A thorough slit lamp examination is
ocular trauma. In this respect, a detailed useful to evaluate the clinical signs may be
history focussed on finding the cause of an helpful to confirm the probable diagnosis.
ulcer in the patient is very important so as to Figure 1 briefly describes the diagnostic
ensure an appropriate management. A approach for acute corneal ulcer.
history of ocular trauma, ocular surgery,

Diagnostic Approach with Corneal Ulcers Patients

Presentation: History
Reduced Visual acuity, tearing, discharge, redness, Pain (disproportionate in case of Herpes and Acanthamoeba)

Risk Factors:
External: Corneal trauma, Contact Lens (CL) wear, contaminated CL solution
Ocular Factors: Ocular surface and adnexal disorders, Dacryocystitis, corneal epithelial disease
Systemic Factors: Long term steroid use, diabetes Mellitus, Kidney Failure, HIV

Slit Lamp Biomicroscopy

Infiltrate Features Severity Factors
Bacterial ulcer: Necrotic stroma, purulent discharge and hypopyon • Size of infiltrate (<2mm or >2mm)
Fungal Ulcer: Stromal Infiltrate with feathery borders • Location of Infiltrate (central Versus peripheral)
Viral Ulcer: Dendritic pattern with progressive geographic and Amoeboid • Depth of Infiltrate (<50% or > 50%)
configuration • Involving limbus, sclera
Acanthamoba Ulcer: Stromal infliltrates with ring shaped configuration and • Associated with AC reaction
hypopyon • Hypopyon

Initial Medical treatment Approach

 Severe ulcers need intense therapy and follow ups
 Anti fungal and Acanthamoeba treatment after smear report and strong clinical judgement

Laboratory Investigation
Conventional Superficial Scraping and Culture Corneal Biopsy and Deep Stromal Confocal Microscopy
Culture
Smear: Giemstain, KOH, Calcoflour White, For Deep Infiltrate For Acanthamoeba and Fungal
Reduced AFB stain eg Nocardia Infection
Culture: Blood Agar, Sabouraud agar, Special Non nutrient
Agar with E. Coli
Figure 1: Diagnostic Approach with Corneal Ulcers Patients

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 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Slit lamp examination starts with:

1. Eyelid assessment for Blepharitis,
meibomian glands dysfunction,
ectropian/ entropian, lagophthalmos.
2. Eyelashes assessment for trichiasis/
distichiasis
3. Lacrimal apparatus system assessment
for punctal abnormalities, dacryocystitis
4. Conjunctiva assessment for discharge,
inflammation, foreign body, papillae,
follicle, cicatrization, symblepharon,
pseudomembrane, filtering bleb, tube
errosion
5. Sclera assessment for any nodule, Figure 2: Post RK bacterial ulcer (S. Aureus) (Image from
Vaishal P Kenia)
thinning
6. Cornea assessment for epithelial defects,
punctate keratopathy, stromal edema,
ulceration, thinning, perforation,
infiltrate characteristics (size, shape,
location, depth), foreign body, sign of
previous corneal surgeries. Fluorescein
or rose Bengal staining allow clinicians
to identify some organism or underlying
cause. For example in cases of viral
infections dendritic ulcers are stained
with fluorescein and rose Bengal stain.
7. Anterior chamber assessment for
presence of any inflammation, look for
cells and flare, hypopyon, hyphema Figure 3: Iron foreign body induced gram negative bacterial
corneal ulcer in a diabetic case (Image from Vaishal P Kenia)
Signs: 6,7
Although there are no specific signs
to identify the responsible organisms, a
careful slit lamp assessment with clinical
experience help reach probable diagnosis.
Various factors such as size, shape, location
of Infiltrate, involvement of limbus, sclera,
associated with AC reaction and hypopyon
gives information about how aggressive the
infection is.
Bacterial:
Gram positive infection (Figure 2):
 Localized infiltrate with distinct borders Figure 4: Fungal ulcer with feathery margin with satellite
 Minimal stromal haze lesion (Image from Vaishal P Kenia)

Gram negative infection (Figure 3):

Fungal:
 Dense stromal suppuration/ Ring
 Dry raised slough, with a dried
Infiltrate
appearance of surrounding cornea which
 Hazy surrounding cornea with a ground
is clear.
glass appearance.
 Stromal infiltrate with feathery edges,

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 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

 Satellite lesions and thick endothelial  Hyopopyon is also a common finding in

exudates, (Figure 4) acanthamoba.
 Sometimes presents with ring infiltrate  In late cases radial keratoneuritis can
 Hypopyon usually forms which is also be noted and can be identified as
convex upwards and may wax and whitish outline of the corneal nerves 6,7.
wane.

Viral:
 Viral ulcers can result from herpes
simplex or herpes zoster infections
 Viral ulcer can be seen in the form of
dendritic pattern (linear branching) due
to central desquamation.
 The end of the branches manifest a
characteristically swollen appearance.
 It generally gets stained with
fluorescence. Figure 6 Ring Infiltrate in Acanthamoeba (Image from Garg
 Anterior stromal infiltrate appear under P., Rao, G., 1999)8
the ulcer but resolves spontaneously.
 Corneal sensation is reduced. B. Microsporadia:
 Progressive centrifugal enlargement  Characterized by raised epithelial lesion
may result in larger epithelial defect and deep stromal keratitis.
with a geographical and amoeboid Identification of causative organism
configuration. (Figure 5) underlying the disease is important for
successful treatment and it requires
laboratory investigations. Microscopic
examination and cultures is a considered as
a gold standard for the accurate diagnosis.
Laboratory investigations allow for direct
visualization of microorganism in material
and help understand the inoculation of
material under appropriate conditions to
allow multiplication of microorganism.
Microbiological Culture and Light
Microscopy:8,9
Traditionally clinicians were heavily
Figure 5 showing three phases of lesions: epithelial dots (9
o'clock), dendritic pattern (6 o'clock) and a geographic epithelial dependent on light microscopes, corneal
keratitis (12–2 o'clock), suggesting herpes simplex virus epithelial smears and cultures. Conventional smear
keratitis.(Image From Gurav P et al 2015 9)
and culture for bacteria, fungus and
Parasitic Acanthamoeba can be prepare by scraping
A. Acantamoeba: the base and leading edge of the corneal
ulcer using flame sterilized Kimura spatula
 Acanthamoba keratitis can be contact
lens or non contact lens related or sterile surgical blade no 15 on Bard
Parker Handle. Every scraping can be use
 Characterized by epithelial irregularities,
for direct microscopic examination, culture
corneal edema, with single or multiple
and antibiotic susceptibility testing. These
stromal infliltrates which has classic
scraping are immediately placed on glass
ring shaped configuration (Figure 6)
slides for light microscopy and agar plates
 However diffuse and satellite infiltrates
for culture (Blood agar, chocolate agar,
are also common.
Potato dextrose agar (PDA), Sabouraud agar

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Vol.10; Issue: 3; March 2020
 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

etc). The slides for light microscopy are With advancement in technology, direct
stained with 10% potassium hydroxide or visualization of pathogens within the
gram stain or Giemsa stain to aid in the patients cornea is possible. In Vivo confocal
visualization of fungal filament, bacterial or microscopy is non invasive technique
Acantamoeba cyst growth respectively. available in clinical settings. To best of our
Special staining such as modified Ziehl knowledge there are presently two
Neelsen for nocardia, microsporadia and modalities available for clinical use are
KOH or calcoflour white staining for scanning slit IVCM (Confoscan, Nidek
acanthaomeba and fungus can be use. For Technology, Fremont, CA) and laser
culture the agar plates are inoculated at 25- scanning IVCM (HRT3 with Rostock
27degree C for 7 days in case of (PDA) corneal module, Heidelberg Engineering,
whereas in case of other media it is Heidelberg, Germany). On confocal
inoculated at 35-37 degree C (2 days for microscopy acanthamoeba cyst can be
blood agar) and microorganism growth is identified as double walled ovoid bodies and
assessed on daily basis. Cultures of contact fungal bodies were seen as bright linear
lens, lens case and contact lens solution can filamentous structures with bright borders
also be done in case of contact lens wearers. that appear as parallel lines (double walled
linear bodies)10
Corneal Biopsy and deep Stromal Treatment protocols
Culture technique: In majority of the cases the infection
Corneal biopsy is indicated if the is resolved without any acute surgical need.
infiltrate is located in the mid or deep However surgical intervention is required
stroma with overlying uninvolved tissues. irrespective of infection is resolved or not
Corneal biopsy can be performed at the slit resolved 2.Initiation of treatment is based on
lamp biomicroscope or operating clinical judgement, smear report and the
microscope. After instillation of topical treatment is modified according to culture
anaesthetic, a small trephine or blade is used report and clinical response. It has also been
to excise a small piece of stromal tissue at reported that use of topical cortico steroid is
the edge of the infiltrate which can be sent controversial hence they are best avoided.
for culture as well as histopathology. Medical Treatment:
Antimicrobial Susceptibility: 9 Antibiotic, antifungal or antiviral
Antimicrobial susceptible testing of eye drops are the treatments of choice
the isolates is performed by Kirby Buaer however Antifungal and Acanthamoeba
Disk Diffusion method using ciprofloxacin therapy started only after microbiological
(5 µg), ofloxacin (5 µg), gatifloxacin (5 µg), evidences, in most cases. The line of
tobramycin (10 µg), chloramphenicol (30 medical treatment and the route of treatment
µg), amikacin (30 µg), gentamicin (10 µg), is decided based on the depth, size and
moxifloxacin (5 µg) as per Clinical and location of infiltrates. Central infiltrate
Laboratory Standards Institute Guidelines. would require more aggressive treatment as
Disk diffusion method assesses antibiotic compared to peripheral, superficial<2mm
sensitivity of bacteria. It uses antibiotic infiltrate. Deep intrastromal infiltrate would
discs to evaluate the extent to which require intrastromal injections as it gives
bacteria are affected by those antibiotics. good drug availability at deeper layer.
Antibiotic susceptibility does not Bacterial Keratitis:
necessarily directly reflex clinical Topical antibiotics (Monotherapy)
susceptibility. can be in given in cases of superficial
Confocal Microscopy: peripheral infiltrates< 2mm. For deep
Confocal microscopy has played a crucial stromal involvement or an infiltrate larger
role in the diagnosis of microbial keratitis, than 2 mm with extensive suppuration a
fungal and acanthamoba keratitis 8,10,11. loading dose every 5-15 minutes followed

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Vol.10; Issue: 3; March 2020
 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

by frequent applications such as every hour involves limbus and sclera. Role of
is recommended. In case of monotherapy, corticosteroid in treating the bacterial ulcer
Levofloxacin 1.5% is preferred over is controversial. The SCUT treatment study
Gatifloxacin and Moxifloxacin due to found no benefit of concurrent topical
emerging resistance with Gatifloxacin and corticosteroid therapy using prednisolone
Moxifloxacin and easier availability of sodium phosphate 1% in conjunction with
Levofloxacin. In cases of large or visually broad spectrum topical antibiotics. A
significant infiltrate or severe infection in pervious study have reported no benefits of
the presence of a hypopyon, topical fortified corticosteroids in managing corneal scars
12
antibiotics is preferred. Systemic antibiotics .Table 2 describes the various antibacterial
are rarely required, however they can be drugs.
considered in severe cases where infection
Table 2 describes the various antibacterial drugs.
Gram Positive Cocci Gram Negative Cocci Gram Positive Bacilli Gram Negative Bacilli
Regular antibiotic Regular Antibiotics Regular Antibiotics Amikacin Regular antibiotic
Cefazolin Ceftriaxone Fluoroquinolone Fluoroquinolone
4th Generation Fluoroquinolone Ceftazidime Clarithromycin F. Tobramycin
Higher antibiotics Fluoroquinolone Higher antibiotics
Vancomycin Amikacin
Linezolid Ceftazidime
Piperacillin
Meropenam
Colistin

Fungal Keratitis:
Fungal ulcers are difficult to treat since the diagnosis is delayed. Mycotic ulcer treatment trial
(MUTT) I compared natamycin and voriconazole revealed that Natamycin had showed
significant clinical improvement as compared to voriconazole. MUTT II compared oral
voriconazole and oral placebo which did report benefits of oral voriconazole in treating
Fusarium Ulcer. Steroids are contraindicated in fungal ulcers. Subconjuctival antifungals
should be avoided since they result in severe pain and induce tissue necrosis to some extent.
Since Intrastromal Voriconazole has a good penetrating capacity it can be considered to treat
deep and larger ulcers. Intrastromal Voriconalzole can be used as an adjunct to Natamycin in
eyes not responding to topical natamycin13,14.Table 3 describes Antifungal drugs6,7. Figure 7
describes the algorithm for managing severe bacterial keratitis.

Figure 7: Algorithm for Managing Severe Bacterial Keratitis

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 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

Table 3 describes Antifungal drugs Causes of Medical treatment failure

Polyenes Pyrimidines Imidazoles
e.g. Nystatin, e.g. Flucytosine e.g. Clotrimazole  Wrong diagnosis
Amphotericin B
Natamycin
Miconazole
Ketoconazole
 Resistance to Antibiotic especially
Fluconazole (Ciprofloxacin, moxifloxacin etc.)
Itraconazole
 Non compliance from patients
Acanthamoeba Keratitis: Surgical treatment
A combination of propamidine isethionate Surgical treatment depends on various
(Brolene) 0.1% and polyhexamethylene factors such as size, location and causes of
biguanide 0.02% can be prescribed in initial the ulcer.
stage. A combination of brolene and Corneal Gluing to manage perforations:
neomycin or monotherapy with For managing corneal perforations
chlorhexidine also gives good results. less than 2mm cyanoacrylate glue is
Steroid should be avoided however in case applied. Healing of the cornea occurs as
of deep vascularisation steroids and fibrovascular tissue grows under the glue
cysticidal agents combination can be used. and dislodges the glue. If the perforation is
Oral Miltefosine can be considered as larger than 2mm then either a tenon patch or
adjunctive treatment for Acanthamoeba multilayer amniotic membrane graft is
keratitis 15. Table 4 describes Antiameoboid considered. It has been reported that
drugs6,7. Gunderson flap have also been use to treat
Table 4 describes Antiameoboid drugs
perforation however it was found to be non
Anticeptic Biocides Aminoglycosides Diamidines effective. 16
Chlorhexidine Neomycin Dibromopropamidine Amniotic membrane transplant (AMT):
PHMB Paromomycin Hexamidine
AMT can provide structural support
Viral Keratitis: in areas of corneal ulceration. The use of a
Usually, about 50% of active epithelial single layered AMT may be sufficient to
lesions heal spontaneously without treat ulcers lacking depth and significant
treatment. The cure rate of antiviral therapy stromal thinning however non effective in
is 95%. In most of the cases healing occur cases of deep ulcers and multilayered AMT
by day 10. After healing has occurred can be considered 16,17.It has been reported
medication should be quickly tapered and that AMT is also efficacious in treating
discontinued by day 14. Steroids are neurotrophic Ulcer 18
contraindicated in viral ulcers. Table 5 DALK using the big bubble
describes the anti viral drugs 6,7. technique seems to be effective and safe in
the treatment of deep fungal as well
Table 5 describes anti viral drug Acanthamoeba keratitis unresponsive to
Topical Systemic medication19. Also, therapeutic Keratoplasty
Acyclovir 3% ointment Oral Acyclovir 400mg
Ganciclovir 0.15% Gel Famciclovir 500mg have shown good results in Acanthamoeba
Trifluorothymidine 1% drop Valacyclovir 1gm keratitis 17. Penetrating keratoplasty (PKP)
Valganciclovir 900mg
is performed in advance cases where
medical treatment fails or perforation too
Supplementary treatment:
large to treat by other options 2,7,16,20
Cylcoplegic agents such as atropine
Novel treatment approaches
sulphate 1%, homatropine 1%, or
Topical Povidone-Iodine 1.25% has
cyclopentolate 1% can be prescribe for three
shown to be as effective as topical
times a day to reduce the ciliary spasm and
antibiotics for bacterial keratitis21. Collagen
produce mydriasis, thus help relieve pain
shields or contact lenses soaked in
and prevent the formation of synechiae.
antibiotics are used in some cases which
Glaucomatous drug can be prescribed to
may enhance the drug delivery. Nano drug
lower the IOP.

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 Vaishal P Kenia et.al. Diagnosis and management protocol of acute corneal ulcer

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International Journal of Health Sciences and Research (www.ijhsr.org) 78

Vol.10; Issue: 3; March 2020