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ARTICLE
Year : 1966  |  Volume : 14  |  Issue : 5  |  Page : 201-208

Clinico cytological study of trachoma and the effect of GS-2989


1 Department of Ophthalmology, Maulana Azad Medical College, New Delhi, India
2 Department of Microbiology, Maulana Azad Medical College, New Delhi, India

Date of Web Publication17-Jan-2008

Correspondence Address:
S.R.K Malik
Department of Ophthalmology, Maulana Azad Medical College, New Delhi
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Malik S, Gupta A N, Deb W C, Sood G C. Clinico cytological study of trachoma and the effect of GS-2989. Indian J Ophthalmol 1966;14:201-8

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Malik S, Gupta A N, Deb W C, Sood G C. Clinico cytological study of trachoma and the effect of GS-2989. Indian J Ophthalmol [serial online] 1966 [cited 2021 Oct 19];14:201-8. Available from: https://www.ijo.in/text.asp?1966/14/5/201/38655

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Whereas the diagnosis of trachoma offers much that is in common agree­ment, the opinion on the usefulness of one or the other of the several drugs is confused and divided and hence the search to find a specific drug against the disease continues.

Recently GS-2989 has been tried by Neema and his co-workers (1964), Pahwa (1965) and Neema and others (1965). The drug belongs to the family of tetracyclines. Its chemical composi­tion is 7 - chloro - 6 - methylene - 6 - demethyl - 5 - oxytetracycline hydro­chloride, no generic name having yet been assigned to the drug. The pre­sent study was carried out to determine the cytological changes in the epithe­lial scrapings and the effectiveness of this drug in cases of trachoma when used locally as 1% oily suspension.


  Material and Method Top


92 cases of trachoma in different stages of the disease were treated with this drug. The clinical and bacterio­logical assessment was done before treatment at weekly intervals during treatment and at the end of treatment. The cytological examination of the conjunctival scrapings taken from the upper palpebral conjunctiva was done before the commencement of treatment and was repeated at 2-weekly intervals till the end of treatment. The cytolo­gical study was done for inclusion bo­dies, specific epithelial changes (e.g. pleomorphism of cells, multinucleated cells, degeneration and necrosis of cells shown by staining changes, cyto­plasmic vacuolation and bearing of nuclei and nuclear division) and the nature of infiltrative cells. The scrap­ings were stained with Giemsa stain.

The drug was used as 1 % oily sus­pension 3 times a day and the cases were followed up for a period varying from 6-12 weeks. The cases studied were graded according to W.H.O. clas­sification of trachoma 1962.

The criteria for recording a cure were:

Elimination of inclusion bodies, dis­appearance of pannus, reversion of cytological changes towards normal and clearance of cellular exudate.


  Observation and Result Top


Out of the 92 cases investigated, 71 were from the urban population and 21 were school-going rural children. 31 cases (33.7%) were found inclusion positive, out of which 11 cases (52.40%) were from the rural group and 20 cases (28.2%) from the urban group. The distribution of the cases according to age, severity of trachoma and presence of inclusion bodies is given in [Table - 1]. The incidence of inclusion bodies was found to be maximum during earlier stages of the disease which went on declining as the cicatrization progress­ed [Table - 2].

[Table - 3] shows the relative fre­quency of cytological changes encoun­tered in this study. It also shows the frequency of these cytological changes in inclusion positive cases. It appears that necrotic and degenerative changes with bare nuclei, multinucleated epi­thelial cells and nuclear and cytoplasmic vacuolation can be taken as cha­racteristic epithelial changes occurring in trachoma.

Significant polymorphonuclear infil­tration was seen in 59 cases. This was constantly present in cases infected with pathogenic bacteria and often in those infected with saprophytic orga­nisms [Table - 4]. Polymorphonuclear infiltration was also seen in 20 cases where secondary infection was not apparent.

Secondary bacterial infection was present in 47 cases (51.0%). The incidence of pathogenic and non-patho­genic organisms and their sensitivity to Penicillin, Streptomycin, Terramycin and chloromycetin are given in [Table - 5]. The occurrence of bacterial infec­tion in different stages of trachoma was practically the same.

In all cases the conjunctival sac was found sterile on a follow-up after one week. Re-infection or its recurrence during treatment was observed in 10 cases (10.9%). This was particularly noticeable in cases of resistant organ­isms. These cases also cleared up after 2-3 weeks of further treatment. At the end of 4 week's treatment no case gave positive growth on culture from the conjunctival swab, even in the case of organisms resistant to either Penicillin, Streptomycin, Terramycin, and/or Chloromycetin.

[Table - 6] shows the effect of treat­ment on inclusion bodies, pannus and cytological and infiltrative changes. The relation between disappearance of inclusion body, pannus and cytological changes is shown in [Table - 7]. The initial change with the treatment is the disappearance of the inclusion bodies followed by resolution of pannus and regression of cytological and infiltra­tive changes.

The overall cure rate after 4 weeks treatment was 59.8%; after 6 weeks 88 and after 12 weeks 92.4%.


  Discussion Top

"Inclusion bodies can be found in 50-80% of fresh cases of active (Tr. I and Tr. II) trachoma if epithelial scrapings are adequately prepared. The incidence of positive results sharply declines in more chronic stages" Sorsby (1964). The incidence of inclu­sion positive cases in this study was found to be 33.7%. This apparently low incidence of inclusion bodies was because of the inclusion of stage 3 and 4 cases in this study. If these cases are excluded the incidence of inclusion positive cases rises sharply (59.4%) and nearly corresponds with that of Pahwa 1965, (54.8%). The overall in­cidence of inclusion positive cases in this study though lower than that of Pahwa (1965) 38.3% is thus fairly within normal limits.

The incidence of secondary bacte­rial infection was 51.0% in this study. Though the nature of infecting organisms in trachomatous and non-tracho­matous cases is very similar, the fre­quency is higher in trachomatous than in normal conjunctiva (Feigenbaum and others 1956). The reported inci­dence of bacterial flora in normal cases is very variable ranging from 13% (Yamazaki, 1958) to 100% (Orsfila and Courden, 1961). Puttana, D'Souza and Bhargava (1958-59) reported an incidence of 28%. Duke-Elder (1965) while analysing the normal conjuncti­val flora reported by various workers found that staphylococcus (60-90%) and diphtheroids (2-33%) formed a vast majority of the organisms present in the normal conjunctival sacs. Other organisms e.g. pneumococci, strepto­cocci, "coliforms" etc. were in insig­nificant proportion i.e. less than 1% to 3%. Feigenbaum and others (1956) found staph. albus and corynbacte­rium pseudodiphtheriae as the most common organisms in trachomatous conjunctivae both occurring singly or in association. Our findings generally agree with above reports except for a higher incidence of staph. pyogenes.

The cytological changes occurring in trachoma have been studied by Tabo­risky (1933), Fassel Feldmann (1941), Thygeson (1955) and Agarwal and Saxena (1955). In our study the cha­racteristic cytological changes seen were pleomorphism of epithelial cells with degenerative and necrotic changes such as poor nuclear staining, nuclear and cytoplasmic fragmentation and va­cuolation with extruded nuclei and large multinucleated epithelial cells. Nuclear division was characteristically seen in several inclusion positive cases.

Besides sulphonamides and chloro­mycetin, tetracycline group of drugs have been frequently assessed for their antitrachomatous value with variable results. Terramycin has been found effective against Trachoma virus by Mitsui and Tanaka (1951), Mitsui and others (1951), Bietti (1953) and Bugarski and Cvetojevic (1954). Leopold (1951) and Siniscal (1952) on the con­trary considered it effective against secondary bacterial infection only.

Good results with Aureomycin have been claimed against trachoma by Braley and Sanders (1949), Boase (1951) and Mitsui and Tanaka (1951). Contrary opinion was expressed by Leopold (1951), Shah (1951) and Siniscal (1952).

Efficacy of Achromycin against tra­choma was claimed by Mitsui and others (1955) and Tsutsui (1955). Agarwal and Malik (1955) however found it of limited value.

Payne (1949), Pijoan and others (1950), Magnol (1950), Shlykova (1956) and Kravtsov (1957) have reported on the effectivity of Chloromycetin against trachoma.

Agarwal and Gupta (1954) and Agarwal et al (1955) have compared the effectivity of sulphonamides, Aureomycin, Chloromycetin, Terra­mycin and Erythromycin on Tracho­ma. [Table - 8] shows the results of various workers.

GS-2989 is a new member of the Tetracycline family. Neema, Nath, Bal & Shukla (1964) used 0.25% oily suspension of the drug and found it effective in 66.7% cases after 4 weeks treatment. Neema, Nath, Bal, Joshi and Shukla (1965) found a cure rate of 88.8% after intermittent topical therapy for 6 months with 1 % oily suspension. Pahwa (1965) reported 70% cure rate after 4 weeks treatment and an inclusion body disappearance rate of 86.8% with 1% oily suspen­sion.

In the present study a cure rate of 59.8% after 4 weeks, 88.0% after 6 weeks and 92.4% after 12 weeks treat­ment with 1 % oily suspension was obtained by continuous treatment. The results of Neema and others (1964) are not comparable as they used 0.25% suspension instead of 1%. Apparently low cure rate found by Pahwa (1965) doubtlessly appears to be due to inade­quate period of treatment. Our cure rate after 4 weeks treatment was much lower, being only 59.8% as against 70% that of Pahwa. Inclusion body disappearance rate was also lower in our study (74.0%) as against 86.8%. This clearly shows that had the treat­ment been continued long enough in Pahwa's series the results would have been much better. On the contrary our results compare more favourably with those of Neema and others (1965). However, it appears that the effect of continuous therapy for 12 weeks is rather more efficacious than that of intermittent treatment for 6 months. It seems beyond doubt that in active cases the results will be better if the treatment is continued till the process has died down completely: it is however, different in late stages of trachoma where the infection is dying down or has already disappeared and the drug is used with a view to prevent reinfection.

Pahwa (1965) reported secondary in­fection in 40% cases while Neema and others (1965) reported it in 56 to 64% of cases. In the present study it was found in 51 %, of the cases. The re­ported cure rate was 83.7% (Neema and others 1965) and 91.6% (Pahwa 1965). In our study, secondary infec­tion cleared in all cases without excep­tion after 4 weeks treatment. Recur­rence occured in 10.9% of cases dur­ing treatment which also cleared off at the end of 4 weeks.

The signs and symptoms were also favourably affected by the drug. The symptoms usually disappeared after 1 week's treatment. Pannus resolved or healed from 2 to 6 weeks depending upon the stage and the age of the dis­ease. The disappearance of pannus closely followed the elimination of in­clusion bodies and preceded the dis­appearance of cytological changes. This sequence is possibly the normal pattern of resolution of pathological changes in this disease with treatment, because

1. The infiltration is more severe and deeper in the subconjunctival tis­sues and tarsus than under the cor­neal epithelium,

2. the penetration of drug deep in the subconjunctival tissues is slower in the lid than in the cornea and

3. as pointed by Thygeson (1951) the superficial infected and degenerated cells are replaced by normal young epithelial cells resistant to inclusion bodies after sometime and in old cicatrical complicated cases where inclusions have permanently dis­appeared, symptoms may continue for sometime after therapy.


  Summary Top


92 cases of trachoma in different stages of the disease were studied clini­cally and cytologically and treated with Gs-2989. The characteristic cytological changes in epithelial cells apart from inclusion bodies were necrotic and degenerative changes, bared nuclei, multinucleated cells and cytoplasmic vacuolation. The characteristic infil­trative cells were mononuclear and macrophages. Polymorphs though pre­sent in the absence of secondary invad­ers appeared abundantly with concom­mitant bacterial infection.

31 cases (33.7%) which were inclu­sion positive became free after 2-12 weeks' treatment. The overall cure rate of trachoma cases in different stages was 92.4%.­

All the cases showing secondary in­fection cleared after 4 weeks treat­ment.

The drug was found to be very ef­fective against trachoma and secondary bacterial infection. The treatment should be continued for at least 12 weeks.[32]

 
  References Top

1.
Agarwal, L. P., Saxena, R. P. and Gupta, B. M. L. (1955) Amer. J. Ophthal. 40, 553.  Back to cited text no. 1
    
2.
Agarwal. L. P.. and Gupta; B. M. L. (1954) Brit. J. Ophthal. 38, 119.  Back to cited text no. 2
    
3.
Agarwal, L. P. and Malik, S. R. K. (1955) Brit. J. Ophthal., 39, 759.  Back to cited text no. 3
    
4.
Agarwal, L. P. and Saxena, R. P. ( 1954) Brit. J. Ophthal, 38, 690.  Back to cited text no. 4
    
5.
Bietti, G. B. (1953). Ibid.. 30, 51.  Back to cited text no. 5
    
6.
Boase, A. J. (1950), Brit. J. Ophthal., 34, 627.  Back to cited text no. 6
    
7.
Braley. A. E. and Sanders, M. (1949), Amer. J. Ophthal. 32, June (part 2), 119,  Back to cited text no. 7
    
8.
Bugarski. G. P. and Cvetojivie, M, (1954) Brit. J. Ophthal. 38, 692.  Back to cited text no. 8
    
9.
Duke-Elder, S. (1965). System of Ophthalmology, Vol. VIII/1 p. 141 Henry Kimpton, London.  Back to cited text no. 9
    
10.
Feigenbaum A., Landau. J. Gurevitch, I and Shamir, R. (1956) Rev. Int. Tra­chome, 33, 363.  Back to cited text no. 10
    
11.
Fassel-Feldmann (1944), Ophthalmo­logica, 101, 74.  Back to cited text no. 11
    
12.
Kravstav. M. P. (1957), Zdrovookler Belor, 6, 47.  Back to cited text no. 12
    
13.
Leopold. I. H. (1951), Arch. Ophthal.. 46, 177.  Back to cited text no. 13
    
14.
Mitsui, Y. and Tanaka, C. (1951), Anti­biot. & Chemother. 1, 146.  Back to cited text no. 14
    
15.
Mitsui, Y., Toya, H., Iwashige, Y., and Yamashita, K. (1951) Arch. Ophthal., 46, 235.  Back to cited text no. 15
    
16.
Mitsui, Y.. Yamashita, K. and Hana­busa, J. (1955), cited by Agarwal & Malik (1955).  Back to cited text no. 16
    
17.
Neema, H. V., Nath. K., Bal, A., Shukla. B. R. (1964), Amer. J. Ophthal. 57, 747.  Back to cited text no. 17
    
18.
Neema, H. V., Nath, K.. Bal, A., Joshi, O. P. and Shuk,a. B. R. (1965), Amer. J. Ophthal. 49, 330.  Back to cited text no. 18
    
19.
Orifila & Courden (1961). Annal. Ocu­list. (Paris) 194, 892.  Back to cited text no. 19
    
20.
Pahwa. J. M. (1965), Orient. Arch. Ophthal. 3, 204.  Back to cited text no. 20
    
21.
Payne, E. H. (1949), New Orleans Med. Surg. J. 101, 597.  Back to cited text no. 21
    
22.
Pijoan. J. Loe, F. & Payne, E. H. (1950). J. Trop. Med. Hyg., 53, 193.  Back to cited text no. 22
    
23.
Puttana. S. T.. D'Souza, C. and Bhar­gava. M. K. (1958-59) Proc. All India Ophthal. Sec. 18, 150.  Back to cited text no. 23
    
24.
Siniscal, A. A. (1952), Amer. Ophthal. 35, 671.  Back to cited text no. 24
    
25.
Shah, M. A. (1951), Brit. J. Ophthal. 35, 50.  Back to cited text no. 25
    
26.
Sorsby, A. (1964). Modern Ophthal­mology Vol. 3 p. 475. Butterworth & Coy. London (Pubishers.)  Back to cited text no. 26
    
27.
Thygeson, P. (1948), Arch. Ophthal.. 39, 695.  Back to cited text no. 27
    
28.
Thygeson, P. (1951), Amer. J. Oph­thal. 34, (2). 7.  Back to cited text no. 28
    
29.
Kimura, S. J. & Thygeson. P. (1955), Amer. J. Ophthal., 39 (2), 137.  Back to cited text no. 29
    
30.
Tahorosky (1933), V. Graefes' Arch. Ophthal. 131, 174.  Back to cited text no. 30
    
31.
Tsutsui, J. (1955), cited by Agarwal & Malik (1955).  Back to cited text no. 31
    
32.
Yamazaki (1958), Acta. Soc. Ophthal. Jap. 62, 1300.  Back to cited text no. 32
    



 
 
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  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8]



 

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