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| ARTICLES |
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| Year : 1982 | Volume
: 30
| Issue : 4 | Page : 323-326 |
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Recent advances in the therapy of ocular mycotic infections
HV Nema, IM Gupta
Department of Ophthalmology and Pathology Institute of Medical Sciences, B.H. U. Varanasi, India
Correspondence Address:
H V Nema
3, Medical Enclave, B.H.U., Varanasi-221006
India
 Source of Support: None, Conflict of Interest: None  | Check |
PMID: 6762350 
How to cite this article:
Nema H V, Gupta I M. Recent advances in the therapy of ocular mycotic infections. Indian J Ophthalmol 1982;30:323-6 |
Considering limitations of available antifungal agents, research and clinical evaluation of newer drugs are constantly being carried out in order to obtain a highly effective, readily available, relatively safe and well tolerated fungicidal drug for the management of mycotic infections of the eye.
This report covers our in vitro and in vivo observations on Pimaricin, Clotrimazole, Econazole, and Thiabendazole for their antimycotic efficacy
| Materials and methods | |  |
The fungi used in the present study were isolated from corneal ulcer cases attending the ophthalmic department of the Institute of Medical Sciences, B.H.U., Varanasi. These included Aspergillus species, Candida albicans, Fusarium species, Penicillium, Alternaria and Curvularia. The isolated fungi were regrown on the standard Czapek Dot's agar medium to obtain pure cultures.
In vitro studies : The antifungal agents in various dilutions (0,1%, 0.2%, 0.25%, 0.4%, 0.5% and 1.0%) were incorporated in Czepak Dot's agar medium after it was autoclaved and cooled down to 40° C. The individual fungal species inoculum was transferred to the centre of the plate. The petri dishes after inoculation were incubated at 25° C for a week and thenceafter the observations were recorded on the basis of the growth or no growth pattern of the fungus in each antimycotic agent, vis-a-vis to the control, wherein no antimycotic agent was incorporated.
In-vivo studies : Aspergillus species and Candida albicans were selected for in-vivo studies on rabbit's eye. Fungus cultures of 48-72 hours duration were used. A homogenous suspension of approximately 10 6sub spores per ml concentration was prepared from Aspergillus colonies, while a loopful of Candida albicans culture was mixed thoroughly in 1 ml. of normal saline. The right eye of the rabbit was used as control and the left as test. After anaesthetizing the cornea, 0.1 ml of fungus suspension was injected into the superficial lamellae of the cornea by 25 hypodermic needle attached to a tuberculin syringe. In the left eye an additional sub-conjunetival injection of antimycotic agent Pimaricin 3 micrograms/ml., clotrimazole 1.5 micrograms/ml., Econazole 1.5 micrograms/ml and Thiabandazole 15 micrograms/ml. was administered. The eyes were examined for watering, discharge, narrowing of palpebral aperture, conjunctival congestion, ciliary congestion, vascularization of the cornea, corneal haze, hypopyon, signs of anterior uveitis and sloughing of the cornea every alternate day for four weeks. The severity of symptoms and signs was graded as nil (-), mild (+), moderate (++) and severe (+-I-+). Then the eyes were enucleated and subjected to histopathological examination with HE, silver methanamine and PAS, staining.
| OBSERVATIONS IN-VITRO | | |
The higher concentration of all the antimycotic agents employed in the present study inhibited the growth of almost all fungi. However, it is noticed that Pimaricin has inhibited the growth of Aspergillus species, Candida species and Fusarium species. Econazole and clotrimazole could inhibit almost all the fungal growths in culture, the latter appears to be more effective. Thiabendazole was effective against Aspergillus and Fuserium but its minimum inhibitory concentration was relative ly higher than the other antimycotic agents. [Table - 1]
| OBSERVATIONS IN- VIVO | | |
In the control eyes infected with Aspergillus species, mild to moderate inflammatory reactions were seen. In 2 eyes, there was severe keratitis while other 2 showed severe keratouveitis with hypopyon. In the control group injected with Candida albicans, 3 eyes showed severe reaction. The eyes were very much congested and developed sloughing of cornea.
In the test eyes, wherein sub-conjunctival fection of antifungal agents were administered soon after the intralamellar injection of fungus suspension, the inflammatory reaction was variable. Generally speaking, the inflammatory reaction was severe in all the eyes injected with Candida albicans as compared to those wherein Aspergillus was inoculated, irrespective of the antimycotic drug used. Mild to moderate clinical and histopathological responses were seen in Aspergillus inoculated eyes treated with Econazole and clotrimazole. Pimaricin treated eyes demonstrated moderate to severe inflammatory rections while Thiabendazole administration could not check the fungal reaction to any appreciable degree either clinically or histopathologically.
Candida albicans caused exceedingly increasing destruction of the rabbit's cornea and in more than 50% of the eyes produced a perforation of the cornea, despite subconjunctival administration of antimycotic agents. The severity of candida infection was striking those eyes particularly treated by Thiabendazole and to a lesser extent treated by Pimarican. Clinically Clotrimazole and Econazole could relatively suppress the fulminating keratomycosis. Noverthless, substantial corneal damage did occur as evident by histopathological examination.
| Discussion | | |
In the present report we have tried to assess the antimycotic efficacy of four promising agents, namely, Clotrimazole, Econazole, Pimaricin and Thiabendazole, both by in-vitro and in vivo studies.
Senstivity tests in vitro demonstrated a high degree of efficacy of both Clotrimazole and Econazole in checking the growth of a number of commonly occurring fungi. Clotrimazole, Econazole, Pimaricin and Thiabendazole were
found to have fungal inhibitory activity in decreasing order. It was found that minimum inhibitory concentration of Clotrimazole and Econazole is remarkably lesser than that of Thiabendazole and Pimaricin. Econazole is one of a large series of substituted phenethylalcohol imidazole with broad spectrum antifungal activity and low mammalian toxicity. Miconazoles a more fully developed drug and is not significantly absorbed when topically applied to the skin or mucosa. Pimaricin also appears to be effective against common ocular fungal invaders. Pimaricin has a wide range of anti-fungal activity against ocular pathogens specially Aspergillus species and fusarium but its penetration, however, is not very good and therefore, its usefulness in deep seated ocular infections is doubtful. Due to the wide spectrum of activity against ocular fungi and its physico-chemical properties Pimaricin appears to be the most promising of the available polyenes for use in oculomycosis. Our in vitro studies confirm such assumptions. Thiabendazole produced inhibition of Aspergillus species, Fusarium and Curvularia species It showed a mild to moderate inhibition.
Our in vivo studies indicated that both Aspergillus species and Candida species are capable of producing severe Keratomycosis following their intra-lamellar inoculation. Ideally animal models do not simulate with the ocular mycotic infections in human beings. Neverthe less, they serve as useful modality for testing the newdrugs. Sub-conjunctival injections of Econazole, Clotrimazole and Pimaricin could suppress the clinical and tissue inflammatory response in the rabbit cornea following experimentally
induced keratomycosis. Both clinical and histopathological reaction in Candida group was more severe than that seen in daspergillus group. It was found that Clotrimazole and Econazole were more effective in checking the reaction as compared to Pimaricin and Thia-bendazole. Thiabendazole was found to be least effective. The poor antimycotic response of these drugs observed in our experimental studies might be explained on the basis of relative inefficacy of these agents against deep corneal infections and secondly in inadequate dosage. Currently we are using these agents topically in the form of suspensions in patients suffering from both superficial and deep keratomycosis. The results of clinical trial may help us to assess the relative usefulness of these agents in future.
| Acknowledgement | | |
Pimaricin, Clotrimazole and Thiabendazole were supplied through the courtesy of Dr. Madan Upadbyay of Ophthalmic Mycology Research Project, Nepal Eye Hospital, Kathmandu (Nepal).
We are thankful to Prof. R.S. Dwivedi, Department of Botany, Banaras Hindu University, Varanasi for sensitivity test.
[Table - 1], [Table - 2]
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