|Year : 1979 | Volume
| Issue : 4 | Page : 9-13
Focal chorioretinitis (Experimental study)
Madan Mohan, G Mukherjee, RK Batta, VM Mahajan
Dr. Rajendra Prasad Centre for Ophthalmic Sciences, New Delhi, India
Dr. Rajendra 'Prasad Centre for Ophthalmic Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Mohan M, Mukherjee G, Batta R K, Mahajan V M. Focal chorioretinitis (Experimental study). Indian J Ophthalmol 1979;27:9-13
|How to cite this URL:|
Mohan M, Mukherjee G, Batta R K, Mahajan V M. Focal chorioretinitis (Experimental study). Indian J Ophthalmol [serial online] 1979 [cited 2020 Oct 29];27:9-13. Available from: https://www.ijo.in/text.asp?1979/27/4/9/32557
The etiological diagnosis of uveitis is largely based on indirect evidence of general, physical and special examinations including laboratory investigations. Inspite of the battery of tests, the etiology remains undetermined in majority and conjectural in others.
Most workers have studied the pathogenesis of experimental uveal lesion by injecting different organisms into the anterior chamber or vitreous cavity. This results in diffuse uveal reaction or an endophthalmitis. In clinical practices, however, uveal lesions are more often focal or disseminated. Granulomatous organismal lesions are almost always focal. Experimental focal lesion simulating the clinical focal uveitis were produced by Mycobacterium tuberculosis, Histoplasma capsulatum and E. histolytica to study their clinical course and pathogenesis. Organisms were innoculated in the supra choroidal space by the technique of Mohan et al.
| Material and methods|| |
Pigmented rabbits of either sex were chosen for experimental studies. They were examined thoroughly to exclude any pre-existing disease. They were divided into the following groups:
Group I:- Supra choroidal Mycobacterium tuberculosis.
Sub-Groups (a) Innoculation of live organism-(5 eves)
(b) Innoculation of heat killed organism- 5 eyes) Left eye was used as control
N. saline (0.1 ml) was injected suprachoroidally.
Group II :- Supra choroidal innoculation of H.
capsulatum (a) Sub groups (i) Live yeast cells-5 eyes
(ii) Live spores -5 eyes
Sub groups (i) Heat killed yeast - 5 eyes
(ii) Heat killed spores - 5 eyes.
Left eye Was used as a control in which 0.1 ml, normal saline was injected supra choroidally.
Group III:- Supra choroidal E. histolytica - 5 eyes Lock's solution along with N.I.H. Media (0.1 ml) was injected in the left eye as a control.
The detailed procedure to prepare the innoculum for mycobacterium tuberculosis series has been described elsewhere (Mohan et al,), so also for HH capsulatum (Mohan et al,).
Method of innoculation: was that described by Mohan et al.
Follow up: Eyes were examined regularly with torch, slit lamp and ophthalmoscopically. Microbiological and histopathological examinations were carried out at regular intervals.
| Observation|| |
Control: In groups I and II normal saline 0.1 ml was injected where as in the group III Lock's solution alongwith N I.H. Media, 0.1 ml was injected as control.
Immediately after injection there was raised greyish white area at the corresponding part of retina. The signs of inflammation increased upto 48 hours and then started regressing. The congestion and oedema disappeared by 96 hours leaving a mild scarring. Clinical course and reactions were similar in all the eyes in the three experimental control groups.
Microbiological and histopathological examinations did not reveal any abnormality.
Group I (a) Innoculation of the live M. tuberculosis Immediately after the injection a localised elevated greyish area appeared corresponding to the site of injection. Signs of inflammation were noticeable in 12 hours which reached its peak on the 6th day with increased vitreous haze. The process of healing with pigmentation was noticed by 4th week [Figure - 1] which was completed by the 12th week.
The organism could be detected from the tissue till 8th day, after that no organism could be demonstrated by culture in L.J. media.
Initially there was homogenous collection of polymorphs [Figure - 2] at the site of lesion upto 8th day, then plasma cells and mononuclear cells collected by 12th day. By 6th week epitheloid cells and giant cells appeared and granuloma formed but there was no cessation. There was complete regression and atrophy of chorioretinal tissue in 12 weeks.
Group I (b) Innoculation of heat killed organisms:
By 24 hours marked vitreous haze appears and visualisation of fundus became difficult. It increased till 72 hours. Thereafter, the media started clearing gradually. The fundus could be visualised on 5th day. It revealed localised retinal oedema and congestion with an ill defined active chorioretinal patch. The reaction started subsiding by 6th day, the margin of the lesion became gradually defined. After 8th day mild pigmentation started and complete healing with scarring occurred by 4th week. Initially there was localised collection of poly morphonuclear cells in the chorioretinal tissue. Mononuclear cells and plasma cells could be seen on 8th day. No organism could be detected. There was complete granuloma formation by 3rd week with collection of plasma cells, epitheloid cells and mononuclear cells. There was no caseation.
Group II: Histoplasma capsulatum
II (a) Live Yeast- The chorioretinal patch developed after the initial reaction on the 4th day with appearance of exudates and retinal oedema. Around the main patch multiple small patches developed in the form of micro-abscess. Vitreous reaction was minimal. The chorioretinal patch increased in size as well as height upto 10th day. After 10th day the lesion became well defined and moderate pigmentation started at the margin. After 14th day the lesion starts regressing. Mild scarring starts in 4th week and lesion becomes more pigmented. Complete healing was noticed by 8th week.
Organism from the lesion could be demonstrated in the lesion upto 14th day.
Initially the lesion starts with collection of inflammatory cells mainly polymorphs and then complete granulomatous lesion developed by 3rd week, characterised by collection of mononuclear cells, plasma cells, giant cells and epitheloid cells. Later on an atrophic chorioretinal lesion developed.
If (b) Live spores: With live spore there was development of anterior as well as posterior-uveitis but the anterior segment cleared within 72 hours whereas the posterior uveitis remained. The lesion was more of a disseminated pigmentary chorioretinal lesion reaching its peak on 12th day. The pigmentary changes were more during healing period. Complete healing occurred by 6 weeks.
No organism could be detected in the aqueous or vitreous.
At the initial phase there was collection of polymorphs and lymphocytes, intracellular organisms [Figure - 3] could be detected upto 14th day. Then it gradually changed to a granulomatous lesion with collection of mononuclear cells and plasma cells.
Group II (c) Heat Killed Yeast- Development of marked anterior uveitis with posterior uveitis from 2nd day onwards. The anterior uveitis starts regressing from 10th day onwards. Well developed chorioretinal patch could be seen after 10th day and it attained maximum height and size upto 3rd week, then gradually regressed a completly healed by 6 weeks. Pigmentary retinal changes were more. No organism could be detected. Non granulomatous lesions with multiple vitreo-retinal traction bands were seen in the histopathological examination.
Group 11 (d) Heat Killed Spores- Initially reactions were almost similar to that of control group but the reaction started subsiding by 3rd day onwards and complete healing by 7 days.
Group III-E. Histolytica
Innoculation of trophozoites into the suprachoroidal space resulted in development of focal chorioretinal inflammation in 24 hours. The height and size of chorioretinal lesion gradually increased till 6th day. Haemorrhages and exudates appeared in and around focal chorioretinal patch. Regression started appearing in and around the lesion. There was focal chorioretinal atrophy with marked scarring and complete healing by 6th week.
Histopathology revealed localised collection of cells mainly in the choroid [Figure - 4] and few in the retinal layers. Initially the cellular reaction was polymorphonuclear and lymphocytic and eosinophillic. Then there was collection of few epitheloid cells, R.B.C. There was marked pigment proliferation with focal chorioretinal atrophy in later stages. Amoebae could be seen only in active stages.
The clinical course of experimental focal chorioretinitis in M. tuberculosis H. capsulatum and E. histolytica has been compared in [Table - 1].
| Discussion|| |
The present experimental study was undertaken to produce focal chorioretinal lesion with different organisms and to study their pathogenesis and clinical course. Intracameral or intravitreal innoculation invariably leads to the production of diffuse uveal reaction and even to endophthalmitis, and thus are unsuitable for such a study. The supra choroidal route has already been successfully used to produce experimental focal chorioretinal lesion with E. histolytica (Mohan et al). The technique of Mohan et al,, was employed for present study. It gives better control to the movements of injecting needle and the lesion can be produced at a desired place. Chances of accidental perforation of the globe as reported by Robert, A. et al, are minimal by the method used in this study.
Innoculation of live M. tuberculosis resulted in development of chorioretinal lesion within 12 to 24 hours which reached its peak gradually by the end off the first week. It starts regressing in the second week and shows complete healing by 12 weeks. Histoplasma capsulatum focal chorioretinal lesion is slow to develop and heals earlier. It developed on 4th day, reached its peak on 10th day and complete healing occured by 8 weeks. E. histolytica, focal chorioretinal lesion developed quickly and pursued a relatively short course. it started within 24 hours, reached its peak by 6th day and complete healing occurred by 6 weeks [Figure - 5] a, b. This shows that there is delayed onset in case of fungal chorioretinal lesion. Similar to other fungal lesions. Tubercular chorioretinal lesion heals gradually and takes longer time for complete healing. Inflammatory reaction was moderate in fungal chorioretinitis as compared to tubercular and amoebic lesions.
Tubercular and histoplasmic chorio-retinitis is moderately exudative. Histoplasmic chorioretinitis in addition shows pigmentary changes in the active phase. Haemorrhages were seen in the active amoebic lesions. Haemorrhages seen in the acute lesions are pathognomonic of amoebic uveitis. It confirms the earlier reports of Braley and Hamilton.
During healing phase there was heavy pigmentation and scarring in amoebic chorioretinal lesion, moderate in fungal chorioretinitis and mild in tubercular lesion. It appears that the live organisms initiate a slow inflammatory response. It is after its death that a severe exudative reaction takes place and it takes longer for complete healing. Early development of the lesion, rapid course and quicker healing after innoculation of killed organisms further prove the above contention. It also seems probable that massive fecal reaction and resultant necrosis is due to toxins/antigen released from the dead organisms rather than to the multiplication of organisms.
The experimental focal chorioretinal lesions produced by the dead M. tuberculosis were more acute and severe in character, appeared early and healed earlier than with live organisms.
Innoculation of live and heat killed yeast did not reveal much differences in the clinical course. Lesions produced by innoculation of heat killed spore were mild and similar to that of control group.
It is well known that fungi can remain dormant or produce only a mild reaction in the ocular tissues. The acute reaction occurs after the organisms are killed by the local defence mechanisms. The acute reactions start around the killed organism. This is amply demonstrated in the eyes in which heat killed organism was innoculated. This exudative reaction, we believe is due to the antigen released from the fungi after it is killed.
The innoculation of live spores which is the usual mode in which this organism enters the tissues produced most fulminating picture with spread to the anterior uvea.
| Acknowledgement|| |
We express sincere thanks to Dr. K.S. Ratnakar, Asstt. Prof. ocular pathology and Dr. (Mrs.) V. Goswamy for their help in histopathological work. We also thank Dr. S.P. Garg and Dr. A. Mazumdar for their help in experimental work.
| References|| |
Braley and Hamilton H.E., 1957, Arch. Ophthal., 58, 1.
Mohan, M, Mukherjee, G., Batta, R.K , 1973, East. Arch. Ophthal., 1, 310.
Mohan, M., Garg S.P., Batta, R.K. and Mahajan, V.M., Experimental Focal Chorioretinal lesion in M. tuberculosis. (under publication).
Mohan, M., Mazumdar, A., Batta R.K. and Goswamy, V., Experimental Focal cborioretinitis with H.O. Capsulatum. (under publication).
Robert, A., Richard, G. and Connor, O., 1968, Arch. Ophthal., 79, 485.
Robert, A., Richard, G. Connor. O., 1970, Arch. Ophthal., 84, 788.
[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]
[Table - 1]