|Year : 1967 | Volume
| Issue : 1 | Page : 11-18
Mycotic infections of the cornea
Minto Ophthalmic Hospital, Bangalore, India
|Date of Web Publication||18-Jan-2008|
S T Puttanna
Minto Ophthalmic Hospital, Bangalore
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Puttanna S T. Mycotic infections of the cornea. Indian J Ophthalmol 1967;15:11-8
After the advent of the topical therapy of various antibiotics and corticosteroids for various inflammatory lesions of the eye, the fungal affections of the eyes are of frequent occurrence as seen from the literature. Thygeson (1953) encountered fungus keratitis after treatment with cortisone and he rightly put it that "Corticosone is a double edged weapon, since, though it may control the inflammation, it may also increase the susceptibility of the individual to micro-organisms". The use of broad spectrum antibiotics and corticosteroid preparations have increased the incidence of mycotic infections of the eye. Even the nonpathogenic fungi have been made pathogenic. Some of the non-pathogenic fungi causing eye lesions are shown in [Table - 1],[Table - 2].
Fazakas (1954) reported positive fungal cultures from the external eye in 25% in healthy eyes and nearly 40% in inflammed eyes. Allen (1963), Anderson et al (1959), Veirs and Davis (1958) were of opinion that antibiotics and steroids favoured fungal invasion of the eye. Haggerty and Zimmerman (1958) have reported a 15 fold statistical increase in mycosis since the introduction of corticosteroids. Gordon and Anderson et al (1959) favour the view that antibiotics and corticosteroids increase the incidence of fungal infections of the eye. Mitsui and Hanabusa (1955) reported an incidence of 67 of fungal cultures in those eyes put on corticosteroids. They showed an incidence of 50` of positive cultures for fungi in eyes treated with topical hydrocortisone for 3 weeks which were fungus free previously. Francois et al (1962) found that uveitis due to fungus was aggravated by corticosteroids.
Majority favour a view that corticosteroids and to a lesser extent antibiotics are responsible for the increase of fungal affections of the eye.
Fungi can invade the eye in the following manners.
1. By direct invasion of the external eye, which is the common path resulting in fungal conjunctivitis, fungal keratitis and fungal infection of the lacrimal passage. Infection may extend to deeper tissues, e.g., various strains of Aspergillus, Candida, Nocardia, Cephalosporium, Actinomyces, etc.
2. Extension from infected neighbouring structures as in fungal dermatitis, nasopharyngitis, sinusitis.
3. May get entry into the interior of the eye by perforating wounds, operating wounds and post-operatively.
4. Haematogenous spread which we often miss specially when they are from occult sites.
5. Suppression of antifungal biological safety mechanism in the conjunctiva.
| Material and Methods|| |
During the routine investigation of common organisms causing corneal ulcers since January, 1960, to December. 1964, 20 cases of mycotic keratitis have been observed. In this investigation routine examination of corneal scrapings from the ulcer stained by Gram's stain, lacto-phenol blue and Periodic Acid Schiff method have revealed saprophytic fungi alone and no bacteria. Cultural methods on potatodextrose agar, nutrient broth, Sabouraud's and Czepk's media produced growth only in fungal media. Conjunctival discharge and lacrimal sac washings were also cultured for evidence of bacteria and fungi.
Animal experiments were conducted on rat's and rabbit's cornea to produce the corresponding lesion to establish whether saprophytic fungi were merely "resident" in the ulcer or were actually causing the lesion pathologically.
Scarification of the cornea with a needle dipped in the culture produced keratitis of varying degree on rats. A 0.01 cc. of platinum loop suspension of the culture in 0.5 cc. of saline was injected into the stroma of the cornea of rat's and rabbit's left eye at the limbus by a tuberculin syringe with 26 gauge needle, to observe the reaction to injection, the right eye kept as control received 0.01 cc. of normal saline.
Fungi isolated from our ulcer series are shown in [Table - 2].
None of our patients had received any previous topical antibiotics or corlicosteroid therapy. They were first seen in the outpatients and later on admitted for investigation and treatment.
The treatment followed in our mycotic ulcer cases consisted of the following in addition to the usual ulcer regime of fomentation. atropine, etc.
(i) Potassium iodide 10 gr. to an ounce orally thrice a day.
(ii) Mycostatin (500000 U) 6 hourly orally for 10 days.
(iii) Four hourly local instillation of two drugs as drops:
(a) 0.125% copper sulphate.
(b) 10% Sodium propionate.
(iv) 0.125% copper propionate ointment locally in the eyes at bed time. The therapeutic results are shown in [Table - 3].
| Discussion|| |
Diagnosis of fungus infection presents a problem specially in its early phase, the diagnostic failure being due to the difficulty of identification by the common methods used for isolation and staining technique, by the slow growth of the fungi on culture media and by the absence of pathognomonic features to differentiate them from more common bacterial and viral infections. Often repeated smears and cultures are essential in coming to a diagnosis, more so in cases of serious uncontrolled corneal ulcers. Not uncommonly smears may be negative, but growth will be seen on culture. In our series two cases which were negative on smear examination, showed growth on culture. Four cases of primary fungus keratitis from India were reported by me (1960) for the first time. Puttana et al (1960) reported 4 cases of primary Aspergillus Keratitis which responded well to the administration of pot-iodide internally and to the local administration of 0.1250% copper sulphate drops and copper propionate ointment locally in addition to mydriatic drops. 1 have also reported (1964) Primary fungus Keratis after instillation of herbal drops suggesting that the fungi might have been carried by the vehicle herbal juice with plant experiments.
A fungus ulcer of the cornea seen after an abrasion or laceration or due to the presence of a foreign body may start as a fluffy white spot soon resulting in a shallow ulcer with a surrounding infiltrate. Soon hypopyon develops. The inflammatory signs are proportionately mild and the tension does not rise in spite of massive hypopyon. The administration of steroids will result in sloughing of the cornea soon ending in perforation with subsequent loss of the eye.
Fungus endophthalmitis is now a well established clinical entity. Fine and Zimmerman (1959) have reported postoperative mycotic endopthalmitis after cataract extraction. The clinical picture starts with a small amount of exudate in the anterior vitreous two weeks after operation. After the initial signs hypopyon appears which may persist or may be transient. Then a severe exudation of stringy and fluffy grayish-white mass spreads in the vitreous. The anterior chamber may become shallow due to vitreous swelling and from inflammatory pupillary block. The steroid therapy at this stage may mask the symptoms though the patient may be aware of severe iritic pain and regression of vision.
The only key to the problem is prevention. Care should be taken to avoid airborne organisms, spores in glove powder, inadequate sterlization of instruments by soaking, contaminated solutions and drugs and fungi in the ocular or periocular tissues of the patient. Routine antibiotic programmes and lavish post-operative steroid therapy should be reorientated and should be used with great caution as both are double edged swords.
Intrastromal injections in the cornea of rats and rabbits showed varying grades of Keratitis ending in perforation in some. Aspergillus flavus Oryza showed mild keratitis though one case ended in perforation. Aspergillus niger produced marked keratitis [Figure - 1] Aspergillus nidulans gave mild Keratitis. Stromal injection gave more severe reactions than scarification. This may be attributable to washing away of the spores by lacrimal fluid and to the poor concentration of spores invading the abrasion produced by scarification.
Aspergillus fumigatus appears to be more toxic in producing keratitis both on rats and rabbits (even on scarification). Positive signs are noticed on the third day after innoculation with penicillium Sp. and Cephalosporium Sp. which were mild in their effect. Fusarium produced a circumscribed ulcer 6 days after injection [Figure - 2]a & b. Rhizopus produced marked keratitis seen 4 days after injection [Figure - 3]. Lasiodiplodia produced marked keratitis with bulging of the cornea seen 8 days after injection [Figure - 4]a & b.
| Therapy of Fungus Infection of the Eye|| |
Amphotericin B and Nystatin are the available potent antifungal drugs at the present time. These are derived from Streptomyces cultures. Neither drug penetrates the eye satisfactorily by any route other than direct intra-ocular injection. Both are highly toxic and should be used with great care. Amphotericin B should not be used in vague and undiagnosed conditions. Weeks or months of treatment may be necessary. Under no circumstances should the total daily dose exceed 1.5 mg/KG of body weight. Therapy is initiated with a daily dose of 0.35 mg/KG and gradually increased as tolerated. Amphotericin B is fungistatic against a wide variety of yeasts and fungi including coccidioides, Histoplasma, Blastomyces and candida. It has no effect on viruses, bacteria or protozoa. Amphoterecin B causes chills, fever, headache and anorexia. Chemical thrombophlebitis may occur, routine check of blood urea, nitrogen levels and periodic kidney function tests are necessary.
| Topical Use|| |
0.3% solution of Amphoterecin B in 5%, glucose or distilled water.
Subconjunctival injection of 125 mg is well tolerated but does not result in appreciable intra-ocular penetration. Intra-ocular injection is extremely toxic. Drops can be used every 15 minutes.
Nystatin is reasonably well tolerated by the eye as a topical ointment containing 200,000 units/gm or by subconjunctival injection of 5000 units suspended in 0.5 cc. saline. Neither method produces measurable intraocular concentrations of Nystatin. Single intravitreal injection of 40 units of Nystatin causes cloudiness of the vitreous persisting for at least a week.
| Other Drugs|| |
Potassium iodide systemically, 0.125% copper sulphate, 10% sodium propionate drops and copper propionate ointment have been tried topically in our series with fairly good results, as shown in [Table - 3]. Only five cases ended in perforation out of 20 cases. Two cases ended in dense corneal opacity with vascularisation.
Corticosteroids favour fungal growth in vivo and hence contraindicated in corneal ulcers. If the corneal ulcer is not responding to the usual antibiotics, it would be better if the therapy is switched on to antifungal agents.
Therapy of intra-ocular fungus infections is not satisfactory and even though the infection is controlled by antifungal agents, intraocular scarring destroys all useful vision.
Therapeutic keratoplasty is indicated in such ulcers showing rapid spread and threatening perforation. The visual results from such keratoplasty leave a great deal to be desired, but the eye is saved from perforation. Successes and failures are on record. It is preferable to control the infection if possible, and then treat the corneal scar with the graft in the absence of active infection. There is always the possibility of fungi reaching the inner eye through the infected cornea to produce resistant endophthalmitis. However, individual cases should be judged by individual merits and handled with careful balancing of the calculated risks.
| Summary|| |
20 cases of corneal ulcers caused by fungi are reported. The fungus was identified both by direct examination of corneal scrapings and by culture.
The human lesions were reproduced experimentally on rat's and rabbit's cornea successfully and the fungus demonstrated in corneal scrapings.
Majority of cases responded well to the administration of potassium iodide internally and to the local instillation of 0.125% copper sulphate drops and copper propionate ointment locally in addition to mydriatic drops. 5 cases ended in perforation. Two cases resulted in dense corneal opacity with vascularization. The available literature has been reviewed.
| Acknowledgement|| |
The author is highly thankful to Dr. V. Subramanyam, Director, Central Food Technological Research Institute, Mysore, for permitting to conduct animal experiments and to Dr. H. C. Srivastava and Miss Zakia Banu for isolation of fungi and to Dr. M. Sirsi, Indian Institute of Science for his help in isolation of fungi and sensitivity tests to antifungal agents. He is also thankful to A. Rao and S. Rao for help in photography, and to Unichem Laboratories for the supply of Copper propionate ointment.
| References|| |
Allen J. H. (1963) as quoted by John, M. Mclean Am. J. Ophth. 56: 537.
Anderson B et al (1959) AMA Arch. Ophth. 62: 169-179.
Fazakas (1953) Ophthalmologica 126: 91: 109.
Fazakas (1954) Ophthalmologica 128: 163-179.
Fine B. S. and Zimmerman L. E. (1959) Amer. J. Ophthal. 48: 151.
Fine B. S. Zimmerman L. E. (1959) Bri. J. Ophthal. 43: 753.
Francosis et al (1962) Ann. Ocul. 195: 97-119.
Haggerty T. E. and Zimmerman L. E. (1958) St. Med. J. 51: 153.
Mitsui and Hanabusa (1955) Brit. J. Ophthal. 39: 244-250.
Puttanna S. T. (1960) Proc. of Trans. Asia-Pacific Acad. of Ophthalmology First Congress 471.
Puttanna S. T. et al (1963) Oriental. Arch. of Ophthalmology: 191.
Puttanna S. T. (1964) Proc, of Trans. Asia-Pacific Acad. of Ophthalmology Second Congress.
Thygeson (1953) as quoted by Y. Mitsui and Hanabusa Brit. J. Ophthal. 39: 244.
Veirs E. R. and Davis C. T. (1958) Arch. Ophth. 59: 172-176 (Feb.)
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
[Table - 1], [Table - 2], [Table - 3]