|Year : 1982 | Volume
| Issue : 2 | Page : 69-75
Berberine in trachoma
Madan Mohan, CR Pant, SK Angra, VM Mahajan
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, A.I.I. M.S., India
Chief organisor and Professor of Ophthalmology Dr. Rajendra Prasad Centre for Ophthalmic Sciences. A..I.I.M.S
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mohan M, Pant C R, Angra S K, Mahajan V M. Berberine in trachoma. Indian J Ophthalmol 1982;30:69-75
Trachoma is as old as recorded human civilization, may be even older. In the present era, trachoma is one of the most widespread of all the eye diseases, affecting approximately 500 million people in the world. It is estimated that about two million of them have been blinded by this disease. In India, trachoma and associated infection is responsible for 20% of economic blindness ([CMR 1974). Trachoma control pilot project was launched in 1956 in India. Though the serious complications and blinding sequelae seem to have been largely controlled, it still remains as one of the major public health problems. The current therapy of trachoma consists of local and systemic use of sulfonamides and anti biotics.2],,
Berberine is the chief alkaloid of Berberis aristata. In the pure form, berberine was clinically tried in patients of chronic trachoma in 1933 by Verma who found its intra conjunctival injections highly effective.
The aim of this study has been to try this indigenous preparations as berberine disodium citratre in cases of active trachoma.
| Materials and methods|| |
Selection of cases-The study was conducted in primary school children aged between 9 to 11 years in rural areas of Delhi. Out of 650 children examined, 190 children (29.23' / ' 0 ) were found suffering from trachoma Stage Ila or IIb. Their tarsal conjunctivae were scrapped and examined for cytological changes.
Collection of Material :
Upper tarsal conjunctival scrapings were collected on sterile cover glass using cover slip technique of Mahajan without topical anaesthesia. Smear was uniformly spread on a glass slide and fixed with methanol. It was stained with freshly prepared Giemsa solution and examined for intracytoplasmic inclusions in epithelial cells under oil immersion. The cytological changes were given a score value from I to 10 using the method of Hardy et a1. 103 out of 190 slides were found inclusion positive.
96 cases were selected for a masked study (24 cases in each group). Clinical para meters of these cases were recorded. The drugs were coded and distributed to the guardians through teachers. Patients were advised to instill the drops three times a day and ointment at bed time in both the eyes for a period of three months. The drugs used were
(i) 0.2% berberine drops and ointment
(ii) 0.2% berberine with 0.5% neomycin and ointment.
(iii) 20% sodium sulfacetamide drops and 6% sodium sulfacetamide ointment.
(iv) Placebo drops (Normal saline) and Placebo ointment (Paraffin base).
Patients were followed up at fortnightly intervals and clinical parameters were recorded at end of each month for three months. Ai the end of study, Giemsa stained smears were examined again. After clinical and microbiological study was over, the data were compiled and drug code was broken.
| Observations|| |
Disappearance of conjunctival follicles, regression or disappearance of limbal and corneal pannus were taken as parameters of clinical cure [Figure - 1]. Microbiological cure rating was based on the scores obtained by the method of Hardy et a1 [Figure 5][Figure 6]. Month wise clinical cure rates in three groups are shown in [Figure - 3]. It can be seen that during the first month cure rates varied between 29.17% in berberine with neomycin group to 33.34% in berberine alone and in sulphacetamide treated groups. Disappearance of various signs of trachoma month wise is shown in [Table - 1].
A comparison of clinical cure and microbiological results is represented in [Table - 2]. The discrepancy between the two is evident. In case of placebo group, the clinical cure was not seen even in a single case whereas microbiological test was negative in 29.16% of cases. No side effects of the drugs were noted. There were however complaints of smarting and burning sensation in sulphacetamide group.
| Discussion|| |
Our study clearly shows that 83.33% patients cured clinically and only 50% became microbiologically negative when they were treated with berberine alone. The response rates were higher i.e. 87.50% and 58.83% in those treated with berberine and neomycin and lower with sulfacetamide. i.e. 72.72% and 40.90% respectively.
This is the first masked clinical study to demonstrate that berberine is effective against trachoma. Earlier, Verma reported clinical cure in chronic trachoma patients by four intra-conjunctival injections of 0.1% of berberine sulfate given at interval of fifteen days. This was confirmed in experiments nearly 40 years later that berberine sulfate in concentration of 0.5 mg could protect the chick embryos from lethal effects of trachoma organisms. They further showed that 0.2% aqueous solution was effective in curing experimentally produced trachoma in monkeys.
From our observations, a number of facts have emerged regarding the efficacy of berberine. Berberine is effective in relieving the symptoms and disappearance of most of the signs within 3 months after its topical use. Sabir and his associates observed that the clinical features subsided in experimental trachoma within 15-18 days with berberine and within 20 days with 20% sulfacetamide drops. No drug reaction was observed in any group. Usually children complained of irritation and burning sensation after application of sulfacetamide ointment and drops whereas no such complaint was found in the remaining groups. In placebo group no clinical cure was seen. Signs and symptoms were seen increasing.
Conjunctival discharge, lid swelling, irregularities of meibomian gland openings, conjunctival oedema, conjunctival hyperaemia, papillary hyperplasia were decreased more in berberine plus neomycin and sulfacetamide treated groups than berberine alone treated group. It might be because of the control of secondary infection which were taken care by neomycin and sulfacetamide. Similar observations were made at the end of second month. However, at the end of third month these clinical features were further reduced in berberine plus neomycin and berberine alone treated groups than sulfacetamide treated group. Preauricular lymph node was seen enlarged in nearly one fourth of the cases in all groups. Even after treatment no significant change in size was observed. In a few cases Bitot's spots were seen and remained unchanged even after therapy.
Though in berberine plus neomycin treated group, microbiological response was the highest at the end of 3 months yet a longer period of follow up and repeated examinations are indicated Microbiological response rates were similar in the remaining two groups. Microbiological result was negative in seven cases of placebo group which tallies with the results obtained in clinically positive cases at the start of the study. Repeated scrapings would have been the answer provided it was practical.
Dutta and Iyer have reported that as hydrochloride, berberine was more potent than as sulfate. Verma used berberine sulfate and reported good results, though his study does not indicate the number of cases. In our study berberine was used as disodium citrate. A study on different salts of berberine against active stage of trachoma is worthwhile.
As regards the duration of treatment, berberine plus neomycin and berberine alone treated groups were observed for the same duration as recommended for antibiotics and sulfa drugs. The duration can be cut short by frequent use of drops or by increasing the percentage of the drug provided it is locally tolerated.
Trachoma is a disease of poverty and a problem of developing countries. Antibiotics are expensive and do not claim cent per cent cure. Anti trachoma antibiotics like chloramphenicol, Terramycin, chlortetracycline, erythromycin and rifampicin are very costly and not suitable for mass treatment. This study shows that berberine combined with neomycin or berberine alone is as effective as sulfacetamide if not more. Since berberine can be adjusted to same pH as tears, no irritation or lacrimation was seen. In concentration used in this study (0.2%), berberine is cheaper. Besides this, berberine on weight basis, is about 100 times more effective than sulfacetamide.
Berberine for prophylactic use is worth a trial in endemic areas of India. Also a long follow up is required to evaluate its affectivity in control of re-infections and recurrences.
Berberine as an effective and relatively less irritable anti trachoma drug is recommended for mass field trials before it replaces conventionally used sodium sulphacetamide and antibiotics.
| References|| |
Gupta, U.C. 1966, Orient. Arch. Ophthalmol. 4 : 5.
Dawson, C.R., Daghyous, T and Mhssadi M, 1974 Arch. Ophthalmol. 92 : 198.
Tarizzo. M.L. and Nata a f. R., 1970, Rev. Int. Trach. 47:7.
World Heath Organisation 1962 Tech Rep. Ser.
Verma, R.L. 1933 Ind. Med. Gaz, 68 : 122.
Mahajan, V.M., 1975 Studies on TRIC Agcnts and their Pathogenicity Ph. D. Thesis, 1975; A,I.I.M.S. New Delhi.
Hardy, D., Surman, P.G. and Howarth W.H. 1967, Amer. J. Ophthalmol. 63 : 1935.
Sabir, M., Mahajan, V.M., Mohapatra, L.N. and Bhide, N.K., 1976, Indian J. Medical Res. 64 : 8.
Dutta, N.K: and Iyer, S.N, 1968, J. Ind. Med. Assoc. 50 : 349.
[Figure - 1], [Figure - 2], [Figure - 3]
[Table - 1], [Table - 2]
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