|Year : 1985 | Volume
| Issue : 5 | Page : 299-302
Ketoconazole : A study in delayed post operative fungal endophthalmitis patients intolerant to amphotericin B
B Lal, PK Agarwal, A Chandra, OP Srivastava
Department of Ophthalmology, K. G. 's Medical College, and Division of Medical Mycology, Central Drug Research Institute, Lucknow, India
P K Agarwal
Department of Ophthalmology, K.G.'s Medical College, Lucknow
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Lal B, Agarwal P K, Chandra A, Srivastava O P. Ketoconazole : A study in delayed post operative fungal endophthalmitis patients intolerant to amphotericin B. Indian J Ophthalmol 1985;33:299-302
|How to cite this URL:|
Lal B, Agarwal P K, Chandra A, Srivastava O P. Ketoconazole : A study in delayed post operative fungal endophthalmitis patients intolerant to amphotericin B. Indian J Ophthalmol [serial online] 1985 [cited 2020 Apr 3];33:299-302. Available from: http://www.ijo.in/text.asp?1985/33/5/299/30735
Fungal endophthalmitis in the delayed post operative phase is well documented,. The present study deals with eighteen cases of delayed post operative fungal uveitis and endophthalmitis, based on response to various antifungal drugs. Ketoconazole is a drug of the recent past and has been found very effective.
| Materials and methods|| |
18 clinically diagnosed fungal endophthalmitis cases were selected for this study. These patients had uncomplicated intracapsular cataract extraction and good visual recovery (6/9 or 6/6). After 6 weeks or more patients complained of photophobia, lacrimation and occasional pain associated with gradual diminution of vision. Examination revealed iridocyclitis with hypopyon in most of the cases and floculent nodules with whitish strands in anterior phase of vitreous. Initially response to local and systemic corticosteroids and antibiotics was obtained but subsequently there was deterioration [Table - 1].
Investigations included swabs from, conjunctival sac and mucosa of the buccal cavity and vagina for culture besides blood and urine cultures. In one case aspirated material from the anterior chamber tap was cultured but it resulted in panophthalmitis. Hence, it was not performed in other patients. Routine haematological & biochemical investigations to rule out diabetes and other systemic diseases were also done. The treatment was categorised in three groups.
1. First line treatment was given in 17 cases for 2 to 4 weeks and consisted of 3.5% potassium iodide drops, atropine eye ointment 1% and nystatin eye ointment (100000 I.U./g) twice daily. In addition, injection Entodon (hexamethyl diamino isopropanol di-iodide) 400 mg or injection Ranodine (methyltrioxyethyl iodoamine) was given on alternate days as 10 injections in gradually increasing doses along with collosal iodine 1 table spoonful orally twice a day.
2. Second line treatment was given in patients where no improvement was noted in 4 weeks by supplementing amphotericin B to the first line of treatment as an initial intravenous does of 0.25 mg/kg dissolved in 500ml of 5% dextrose solution in water over 3 to 6 hours. The subsequent daily dose was gradually increased by 0.1 mg/kg body weight until the dose reached 1 mg/kg or the development of toxic reactions necessitated its withdrawal. The main reactions in the present cases were chills and faver (40°C) in almost every case. In two cases an anaphylaxis resulted and in one case skin rashes were found. 6 patients had decreased renal functions. However, these changes were found to be reversible on the cessation of therapy.
3. Third line treatment consisted of the first line treatment and oral ketoconazole 400 mg daily after meal for a period of 3 months.
| Assessment of response|| |
A. Good Response
i. Control of signs & symptoms of iridocyclitis i. e. regression of aqueous flare, hypopyon, photophobia and lacri mation.
ii. Regression of signs and symptoms of inflammatory response.
iii. Regression of vitreal haze.
iv. Visual improvement upto the extent of 6/6 or better.
B. Poor Response
If the above were not achieved.
| Observations|| |
The results of smear and culture are shown in [Table - 2].
Aspirate from the anterior chamber tap was positive for Candida abicans in one patient and C albicans was grown from blood in 7 and from buccal cavity and vagina in 4 patients each. [Table - 3] shows the response to various threapeutic protocols. Amphotericin B was helpful in 4 cases, its toxicity was the limiting factor in the remaining 12. Oral ketoconazole was useful in 8 cases. In one patient the eye was lost due to panophthalmitis and one case improved by vitrectomy. The results of heamatological and biochemical investigations were non contributory.
| Discussions|| |
The details of lesions studied in 18 patient in this study brought out a definite clinical picture which was similar to the one pointed out by Fine and Zimmerman and Theodore et at. It is not generally realized that delayed infections following cataract extraction are often due to fungi of low pathogenicity.
The relatively slow progressing fungal endophthalmitis resembles post operative iridocylcitis of endogenous origin or low grade bacterial infection.
The long term therapy of antibiotics and corticosteroids is not only ineffectual but may actually promote the growth of fungus and it's extension throughout the vitreous. The outcome of therapy is usually poor by the common antifungal drugs. In this series oral ketoconazole played a key role in comparison to amphotericin B. Till now ketoconazole has been used in experimental situations and its use in clinical setting is a new advance. Much stress has been laid on clinical presentation by various workers because in many instances fungus cannot be isolated. The anterior chamber aspiration which was attempted in our first case was positive but proven deleterious. Cultures from blood and buccal cavity vagina, though positive in eleven patients in the current study do not establish a definite fungal aetiology for endophthalmitis.
Iodine preparations are known to possess antifungal activity and have been used in the past for keratomycoses Since specific antifungal drugs were not freely available for general use of patients, our usual choice fell on iodine preparations for the initial treatment. However, it proved useful in only 1 case out of 17. Only 4 cases out of 16 tolerated the full course of i. v. amphotericin B therapy and improved. In the remaining 12 (75%) cases the drug had to be withdrawn due to side effects, like chills' fever and renal impairment. Since the visual improvement was poor ketoconazole was tried in 11 patient and 8 patients were cured. At present clinical data for ketoconazole treatment of fungal endophthalmitis is not available except the present study and Green et a1 have found its usefulness in experimental endogenous Candida endophthalmitis.
Fungal etiology could be established in only one case in which anterior chamber tap aspiration was done. It proved hazardous and was not tried in other cases. Indirect evidence in the form of positive buccal, vaginal and blood cultures were there in half the cases. In rest of the the fungal etiology was presumed on the basis of clinical judgement i. e. determination of signs and symptoms by administering antibacterial therapy and response to antifungal therapy.
| Summary|| |
Eighteen cases of delayed post operative fungal endophthalmitis were studied. Follow up therapy could be done in 17 patients.
Initially, one case responded to 1st-line treatment by local and systemic iodine therapy. Subsequently, atmphotericin B was given intravenously and good response was obtained in 4 patients who tolerated it. Oral ketoconazole was successful in 8 out of 11 patients and one case improved with vitrectomy.
| References|| |
Fine, B.S. and Zimmerman, L.E., 1959, Amer, J. Ophthalmol. 43: 753.
Michelson, P. E., Stark., Reeser, F. and Green, W,R., 1971, Int. Ophthalmol Clin, 11,: 125,
Green, M.T., Brobery Jones, P.H. and Gentry, L.O., 1979, 11th international Congress of Chemotherbpy and 19th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston Massachusetts 1-5 October 1979, p. 143.
Theodore, F.H., Littnman, M.L,, and Almeidia. E , 1961, Arch Ophthalmol. 66 863.
Suie, T. and Havener, W,H., 1963, Amer, J, Ophthalmol, 56: 63.
[Table - 1], [Table - 2], [Table - 3]