Condition category
Ear, Nose and Throat
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The first line of treatment for fungal corneal ulcers in the eye is natamycin eye. Generally such ulcers heal within 2 weeks. If they do not heal in 10-14 days another anti-fungal drug is used, such as voriconazole eye drops. However, the eye drops may not penetrate a deep lesion. Hence the aim of this study is to find out whether the injection of voriconazole into the eye is more effective than addition of another eye drop such as voriconazole in cases not responding to conventional antifungal therapy.

Who can participate?
Patients aged over 18 with fungal corneal ulcers not showing any signs of improvement after two weeks treatment with natamycin eye drops.

What does the study involve?
Participants will be randomly allocated into two groups. One group will be treated with voriconazole eye drops while the other group will be treated with voriconazole injections into the eye.

What are the possible benefits and risks of participating?
The benefits of enrolling are the treatment of the ulcer and the risks are slight pain and perforation of the ulcer. With both voriconazole eye drops and voriconazole injections there may be transient visual hallucinations which are reported rarely.

Where is the study run from?
Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (India).

When is study starting and how long is it expected to run for?
The study ran from December 2008 to June 2010.

Who is funding the study?
Dr Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (India).

Who is the main contact?
Namrata Sharma, MD, DNB, MNAMS

Trial website

Contact information



Primary contact

Dr Namrata Sharma


Contact details

Dr Rajendra Prasad Centre for Ophthalmic Sciences
All India Institute of Medical Sciences
Ansari Nagar
New Delhi
+91 11 2659 3144

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Comparative evaluation of topical versus intrastromal injection of voriconazole as an adjunct to natamycin in recalcitrant fungal keratitis: a randomised controlled trial


Study hypothesis

In cases of fungal keratitis who do not respond to natamycin, voriconazole is usually added. This can be given as topical eye drops or may be given in the form of injection. When injected intra-corneally, i.e. at the site of the lesion as targeted drug delievery , it may be be more effective. In addittion, the problems of compliance with topical eye drops are also addressed here.

Ethics approval

Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences (AIIMS), India, 30/11/2008

Study design

Randomized controlled clinical trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Fungal corneal ulcer, fungal keratitis


Forty eyes of forty patients randomized into two groups of 20 patients each.

Group 1:
Topical 5% natamycin eye drops 4 hourly, 0.3% ciprofloxacin hydrochloride eye drops four times a day, 2% homatropine eye drops and 1% voriconazole eye drops prepared by ocular pharmacology by reconstituting injection voriconazole 200 mg powder in 19ml ringer lactate to instill 1 hourly round the clock for 48 hours followed by tapering of drug.

Group 2:
Patients randomized to intrastromal injections were taken to the operating room. Injection voriconazole 200mg powder reconstituted with Ringer lactate to obatin 50µg/0.1ml solution.
Injections were repeated 72 hours apart. Patients in this group also received topical therapy with 5% natamycin 4 hourly, cycloplegics and 0.3% ciprofloxacin hydrochloride 6 hourly.

Intervention type



Not Applicable

Drug names

Atamycin, voriconazole

Primary outcome measures

Best Spectacle Corrected Visual Acuity (BSCVA) 3 months after intervention.

Secondary outcome measures

Time to healing

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Patients with a smear or culture proven fungal ulcers
2. Ulcers greater than 2mm in size, involving more than one-third of the stromal thickness and not showing any signs of clinical improvement after two weeks of natamycin
3. Patients who were willing to be treated as an inpatient, willing to follow up regularly, and return for medications regularly every 48-72 hours

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Patients with mixed infection on smear or culture, evidence of herpetic keratitis on history or examination, impending perforation, bilateral ulcers, those with vision less than 6/60 in the other eye, pre-existing scar not distinguishable from the new ulcer
2. Those less than 18 years of age

Recruitment start date


Recruitment end date



Countries of recruitment


Trial participating centre

Dr Rajendra Prasad Centre for Ophthalmic Sciences
New Delhi

Sponsor information


Dr Rajendra Prasad Centre for Ophthalmic Sciences (India)

Sponsor details

All India Institute of Medical Sciences
Ansari Nagar
New Delhi
+91 11 2659 3144

Sponsor type

Hospital/treatment centre



Funder type

Research organisation

Funder name

Dr Rajendra Prasad Centre for Ophthalmic Sciences (India)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes