Year : 1970 | Volume
: 18 | Issue : 3 | Page : 111--117
Study of red blood cell morphology and abnormal haemoglobin in the causation of Eales' disease and other vitreous haemorrhages
IS Jain1, GS Kanwar1, KC Das2,
1 Department of Ophthalmology, Postgraduate Institute of Medical Education, & Research, Chandigarh, India
2 Department of Haemotology, Postgraduate Institute of Medical Education, & Research, Chandigarh, India
I S Jain
Department of Ophthalmology, Postgraduate Institute of Medical Education, & Research, Chandigarh
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Jain I S, Kanwar G S, Das K C. Study of red blood cell morphology and abnormal haemoglobin in the causation of Eales' disease and other vitreous haemorrhages.Indian J Ophthalmol 1970;18:111-117
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Jain I S, Kanwar G S, Das K C. Study of red blood cell morphology and abnormal haemoglobin in the causation of Eales' disease and other vitreous haemorrhages. Indian J Ophthalmol [serial online] 1970 [cited 2021 Jun 13 ];18:111-117
Available from: https://www.ijo.in/text.asp?1970/18/3/111/35074
Since the time of Henry Eales, who first described the condition in 1880 the etiology of so called Eales' disease still remains an enigma. From time to time various theories have been put forward for its causation: Tuberculosis and tuberculo-allergic processes - Axenfeld and Stock  . Thromboangitis obliterans - Marchesani  , Focal sepsis - Applemann  , Werner , Puttana  , Endocrinal dysfunction - Jeandelize  , Mawas and Herschberg  and Diseases of the haemopoetic system - Donner  , Mawas  .
Changed red cell morphology, Kahn, Kahan and Benko  these authors reported thorny red blood cells (acan.thocytes) in the peripheral blood of a case of Eales disease. The chance finding of acanthocytes by one of us (I. S. Jain) in a case of Eales disease, made us feel to undertake systematic study to evaluate the role of acanthocytes vis-a-vis tubercular allergy, which is the most widely accepted etiological factor.
Material and Methods
Thirty three cases of Eales' disease were studied from January, 1967 to November, 1968; in the eye Department of the Postgraduate Institute of Medical Education and Research, Chandigarh.
Detailed ocular and systemic examination and routine investigations including Mantoux Test were carried out in every case.
Special investigations for abnormal Red Blood Cells in peripheral blood smear, and abnormal haemoglobin, were also done in every case.
For control, thirty five cases of vitreous haemorrhages due to known causes, were studied for any evidence of acanthocytes in their peripheral blood.
Twenty five cases of Mantoux positive not suffering from vitreous haemorrhages, and likewise, 25 mantoux negative children suffering from various diseases in paediatric wards of our Hospital were studied for any evidence of acanthocytes.
Mantoux test results were studied in 25 random samples of normal pipulation to compare with Mantoux results in Eales disease cases.
Fifty proved cases of tuberculosis (proved clinically, radiologically and having positive sputum for Acid Fast bacilli), from the chest clinic of the Postgraduate Institute of Medical Education and Research, Chandigarh were studied for any evidence of acanthocytes in their peripheral blood.
One hundred normal healthy persons, taken from the staff of the eye department and persons reporting for refractive errors, were also screened for any evidence of acanthocytes in their peripheral blood.
Total fat and lipoprotein studies were done in 14 cases, to demonstrate any association with positive and negative acanthocyte cases. Demonstration of Acanthocytes: was done by two methods:
(1) Examination of "Dry blood film" stained by Leishman's Stain.
(2) "Wet blood film study".
One drop of blood, diluted with four drops of saline, covered with a coverslip was examined under the microscope.
5% or greater, incidence of acanthocytes in the blood film was considered as positive case for acanthocytosis.
Estimation of foetal Haemoglobin was done in every case by the method of Singer and Chernoff  .
Age and sex incidence
There were 31 males and only two females. No patient was under 10 years of age; two were between 11-20 years and 19 were between 21-30 years while 12 were between 31-40.
There was no , evidence of focal sepsis in thirty patients, while only three patients had evidence of dental caries.
One case showed giardiasis, another showed cysts of lodomoeba Butschli and the third ova of H. Nana. Rest of the thirty cases showed no intestinal parasites.
Only three cases showed evidence of old or active luug involvement; in the rest of the thirty cases respiratory system was normal. No evidence of liver enlargement was found in any of the: 33 cases of Eales disease.
This table shows no appreciable difference between the cases of Eale's and that of normal persons.
Abnormal haemoglobin: None was detected in any of the 33 cases of Eales' disease.[Table 2],[Table 3],[Table 4]
Blood lipid studies
Total fat, cholesterol, phaspholipid, total serum proteins, albumin, alpha  , alpha, and Beta and gamma globins, lipoproteins - alpha and beta and non-esterified fatty acid - estimations were within normal limits in cases of Eales' disease with acanthocytes and Mantoux positive and other cases of Eales with acanthocyte negative.
Thus no change was noted in lipid studies in acanthocyte positive cases of Eales disease.
Most of the authors have blamed tuberculosis as the cause; Axenfeld  , found 8 cases of periphlebitis retinae in 284 cases of pulmonary tuberculosis while Elliot , found active or healed pulmonary tuberculosis in 35% of his 31 cases of Eales and from India Awasthe, Mehrotra and Shrivastava  , reported an incidence 1.3% of Eales, out of 1180 untreated pulmonary tuberculosis. In the present series, out of a study of 50 cases of proved tuberculosis none was detected to have Eales disease. Evidence of tuberculo -allergic process has been noted by many authors Appleman  , Elliot, , Gupta  , Ashton  , Chanda  . The incidence of Mantoux positive in the present series of Eales cases is also very high 88% (29/33) cases.
Hagino  has recently put forward a positive experimental evidence for tubercular allergy by B. C. G. vaccination sensitisation in rabbits. Pahwa  also reported seeing one case of vitreous haemorrhage following B. C. G. vaccination.
No significant role of other etiological factors like, focal sepsis and intestinal parasites could be: established in the present series.
Role of Acanthocytes
Acanthocytes are small irregularly shaped red blood cells with spur like processes of variable length at irregular intervals. [Figure 1],[Figure 2],[Figure 3]. So far, acanthocytosis has been recognised as a congenital abnormality of the R. B. C.'s commonly seen in cases of atypical retinitis pigmentosa, having steatorrhoca with absent or markedly reduced plasma beta lipproteins. Acanthocytosis has also been found in association with hereditary vitreoretinal degeneration. This abnormality of the red cells is possibly due to a mutant recessive gene, which when inherited from both parents, produces the homozygous state of acanthocytosis.
Acquired acanthocytosis has recently been observed in a case of Eales disease by Kahn et al.  They lacked confirmation of their observation. From our systematic study to evaluate the role of such abnormalities of the R. B. C. in cases of Eales disease, the following observations and inferences are discussed:
We have taken acanthocytes positive only when the percentage of acanthocytes was 5% or more.
In the present series, we have 9 positive cases (5-50% Acanthocytes) at the time of our examination.
During a random sampling of the general population attending the eye outpatient department we found only 3 positive cases out of 100 normal cases. These cases were not suffering from any intraocular disease. Most of the Eale's disease cases in our series were also Mantoux positive (29/33).
Since tubercular allergy is by far the commonest etiological agent, responsible, for the so called Eales cases, it was thought pertinent to look for this erythrocytic abnormality in cases having frank pulmonary tuberculosis but no ocular involvement. In 50 proved pulmonary tubercular cases 5 patients were found having acanthocytes. While in 25 cases having only evidence of tubercular allergy namely Mantoux positive cases) we found 5 patients (20%) having acanthocytes in their peripheral blood.
Incidentally it is appropriate to emphasise that the first case of acquired acanthocytosis reported by Kahn et al  was also found to be in a case having tubercular background.
Evidence of acanthocytes in 25 Mantoux negative cases; was found in only two persons (8%). From this it appears that there is obviously an increased incidence of acanthocyte positive cases in individuals who were having tubercular allergy. Out of three cases having focal sepsis, one case was positive for acanthocytes, but this case was also Mantoux positive.
Kahn et al  produced transient acanthocytosis within two hours after injecting pyrexal intravenously: (Pyrexal - Wander, is 0.3 g. purified endotoxin prepared from salmonella abortus equi) which disappeared again after two hours. The pyrexal acted as an artificial toxin analogus to the endotoxin liberated by bacterial infection in the body. This experimental evidence by Kahn et al  may also explain that increased incidence of acanthocyte positive cases (9/33 - 27.3%) in the present series, could be induced by the tubercular protein toxins in these cases. This phenomenon was certainly not of lasting duration, as it showed fluctuations on follow up examination and a few cases even became negative later.
It is quite probable that many other cases would also have been acanthocyte positive, if they had come for examination at that critical stage when this abnormality of the R. B. C. would have been maximum and had precipitated the visual catastrophe. It is also possible that various forms of treatment previously tried by these patients before presenting themselves to us e.g. corticosteroids, antitubercular therapy etc. might have helped in reversing this peculiar abnormality of the R. B. C.
Meehanism of production of vitreous haemorrhage by Acanthocytes
1. These abnormal R. B. C. show increased mechanical fragility.
2. The toxins cause changes in the vessels and hyaloid membrances of vitreous body.
3. The mobility of these abnormal cells is limited to rotating with each other like cogwheels and thus can easily block the vessels because of mechanical hindrance.
This study therefore suggests that both clinical picture of Eales disease and the phenomenon of acquired acanthocytcsis may be due to endotoxin of tubercular protein or other endotoxins.
Summary and Conclusions
The present study was undertaken to evaluate the role of red cell morphology (Acanthocytosis) in the pathogenesis of Eales disease.
Abnormal haemoglobin was not found to play any role in its causation. Acquired acanthocytosis was observed in 27.3% of cases of Eales disease, which was fluctuating in duration and it is suggested that this phenomenon may be induced by endogenous toxins principally tubercular proteins.
Intestinal worm infestation and focal sepsis were not considered to play a significant role in the causation of Eales disease.
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