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   Table of Contents      
ARTICLE
Year : 1967  |  Volume : 15  |  Issue : 1  |  Page : 11-18

Mycotic infections of the cornea


Minto Ophthalmic Hospital, Bangalore, India

Date of Web Publication18-Jan-2008

Correspondence Address:
S T Puttanna
Minto Ophthalmic Hospital, Bangalore
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Puttanna S T. Mycotic infections of the cornea. Indian J Ophthalmol 1967;15:11-8

How to cite this URL:
Puttanna S T. Mycotic infections of the cornea. Indian J Ophthalmol [serial online] 1967 [cited 2019 Dec 9];15:11-8. Available from: http://www.ijo.in/text.asp?1967/15/1/11/38672

Table 3

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Table 3

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Table 2

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Table 1

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Table 1

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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 Top


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 Top


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 Top


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 Top


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 Top


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 Top


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 Top


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.[14]

 
  References Top

1.
Allen J. H. (1963) as quoted by John, M. Mclean Am. J. Ophth. 56: 537.  Back to cited text no. 1
    
2.
Anderson B et al (1959) AMA Arch. Ophth. 62: 169-179.  Back to cited text no. 2
    
3.
Fazakas (1953) Ophthalmologica 126: 91: 109.  Back to cited text no. 3
    
4.
Fazakas (1954) Ophthalmologica 128: 163-179.  Back to cited text no. 4
    
5.
Fine B. S. and Zimmerman L. E. (1959) Amer. J. Ophthal. 48: 151.  Back to cited text no. 5
    
6.
Fine B. S. Zimmerman L. E. (1959) Bri. J. Ophthal. 43: 753.  Back to cited text no. 6
    
7.
Francosis et al (1962) Ann. Ocul. 195: 97-119.  Back to cited text no. 7
    
8.
Haggerty T. E. and Zimmerman L. E. (1958) St. Med. J. 51: 153.  Back to cited text no. 8
    
9.
Mitsui and Hanabusa (1955) Brit. J. Ophthal. 39: 244-250.  Back to cited text no. 9
    
10.
Puttanna S. T. (1960) Proc. of Trans. Asia-Pacific Acad. of Ophthalmology First Congress 471.  Back to cited text no. 10
    
11.
Puttanna S. T. et al (1963) Oriental. Arch. of Ophthalmology: 191.  Back to cited text no. 11
    
12.
Puttanna S. T. (1964) Proc, of Trans. Asia-Pacific Acad. of Ophthalmology Second Congress.  Back to cited text no. 12
    
13.
Thygeson (1953) as quoted by Y. Mitsui and Hanabusa Brit. J. Ophthal. 39: 244.  Back to cited text no. 13
    
14.
Veirs E. R. and Davis C. T. (1958) Arch. Ophth. 59: 172-176 (Feb.)  Back to cited text no. 14
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]
 
 
    Tables

  [Table - 1], [Table - 2], [Table - 3]



 

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  In this article
Material and Methods
Discussion
Therapy of Fungu...
Topical Use
Other Drugs
Summary
Acknowledgement
References
Article Figures
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