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ARTICLES |
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Year : 1973 | Volume
: 21
| Issue : 3 | Page : 102-107 |
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Topical corticosteroid and intraocular pressure in high myopia. I. Study of pressure response
SK Amba, IS Jain, SD Gupta
Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
Correspondence Address: S K Amba Department of Ophthalmology, Postgraduate Institute of Medical Education and Research, Chandigarh India
Source of Support: None, Conflict of Interest: None | Check |
PMID: 4499999
How to cite this article: Amba S K, Jain I S, Gupta S D. Topical corticosteroid and intraocular pressure in high myopia. I. Study of pressure response. Indian J Ophthalmol 1973;21:102-7 |
BECKER AND HAHN[4] and ARNIALY [1],[2],[3] postulated a genetic basis for the intraocular pressure response which follows the topical administration of corticosteroids over a period of four to six weeks. Three levels of response were described viz. homozygous high responders (gg), heterozygous, moderate responders (ng) and homozygous poor responders (nn). According to these authors the steroid provocative test gave an impressive tool in the hand of ophthalmologist to investigate proneness to glaucoma or carrier state of glaucoma gene in a subject. It was also suggested that it may be possible to find other genetic factors which are linked to glaucoma in the same chromosome.
This genetic basis of steroid response led various authors to study the effect of topical corticosteroids in patients with other types of glaucoma or conditions related to glaucoma. One such condition is diabetes, where primary open angle glaucoma occurs more frequently. It had also been observed by various authors that intraocular pressure was lower is diabetics with retinopathy. [6],[13] This relationship between intraocular pressure and diabetes prompted, BECKER [5] and GILL AND JAIN[9] to study the effect of topical corticosteroids in a larger series of diabetics. The results demonstrated a significantly higher prevalence of pressure elevation in diabetics without proliferative retinopathy. Thus, it was postulated that steroid provocative test in young diabetics might help to predict development of proliferative retinopathy well in advance.
Another condition related to glaucoma is myopia where chronic simple glaucoma is quite common. JAIN et al [12] had observed that myopic refractive error of 5 D or more exercised a beneficial effect on the severity and course of diabetic retinopathy. It was thought that this beneficial effect might be due to the presence of glaucoma gene in such patients. A genetic linkage between chronic simple glaucoma, myopia and diabetes was thus postulated. PoDos et al [16] reported a higher prevalance of steroid responders in high myopia in a study on seventeen patients. The value of steroid provocative test in diabetics encouraged the present authors to study the results of this test in a large series of high myopes.
Material and Methods | | |
Fifty cases of myopia of more than 6D, having clinically normal eyes, with no history of glaucoma in the family were selected. Each subject had a complete eye examination including Schiotz tonometery using two weights method and correcting the tension by Friedenwald's nomogram (1955). Gonioscopy, perimetry and water drinking provocative tests were done wherever indicated to rule out the presence of chronic simple glaucoma. Each subject was then asked to use betamethasone 0.1% topically (Betnesol `N' eye drops - Glaxo) applied, to one or both eyes, four times a day for a maximum period of six weeks. Tension was recorded once a week in the morning time between 9.00 AM to 12.00 noon. Topical application of the drug was stopped earlier, if the eyes showed a rise of more than 16 mm of Hg or attained a tension of 31 mm or more and the subject was followed till the tension returned to normal. In 16 subjects steroid drops were used in one eye only while in the rest of subjects they were used in both the eyes.
To compare the results in normal population, thirty subjects of refractive error upto ± 4 D, considered to be the normal physiological variation, were subjected to local betamethasone and followed in a similar manner.
In all 77 eyes of the high myopes and 50 eyes of the control group were studied. The response obtained was classified on the basis of rise of tension as follows:
Observations and Results | | |
High Myope Group:
The sample consisted of 50 subjects, 26 males and 24 females with ages ranging from 14 years to 80 years and of myopic refractive error of 6 to 22 D. The mean intraocular pressure was 16.24 mm Hg with SD 2.69. Seventy-seven such eyes were subjected to the steroid provocative test. There were 9 eyes which showed IOP of 20 mm or above. When charted as frequency curve, it conformed to a bell shaped curve [Figure - 1]. On steroid treatment, intraocular pressure showed a rise in a significant number of eyes in the 4th week. The mean intraocular pressure in the 4th week was 20.82 mm Hg showing a mean rise of tension of 4.78 mm Hg (p < 0.01). The frequency curve at this stage did not conform to bell shape but rather showed a shift to 20-21 mm level and another small rise at 28-29 mm level [Figure - 2]. Considering the magnitude of rise of tension, 27 eyes (350) had shown a rise of 6 mm or more. There were 3 eyes which had shown a rise of more than 16 mm or attained intraocular pressure of 31 mm Hg. Medication in these eyes was discontinued and the subjects followed till the intraocular pressure came to original level.
Further medication showed a further steady rise of intraocular pressure. In the sixth week the mean intraocular pressure was 22.96 mm Hg showing a significant rise in tension of 6.72 mm (P < 0.01). Frequency curve [Figure - 2] at this stage became irregular and showed a rise at 24-25 mm and another at 31 mm and above. Considering the magnitude of rise of tension, 46 eyes (60%) showed a rise of tension of 6 mm or above [Table - 1]. On classification of rise, intraocular pressure response based on pressure difference [Table - 1] 48% could be classified moderate responders and 12% as high responders. Seven out of seventeen subjects in whom steroids were applied in one eye only showed a rise of intraocular pressure of 1-6 mm Hg in the untreated eye. These subjects showing a contralateral response could be classified in one of the responder groups.
Control Group:
Control group consisted of 30 subjects, 16 males and 14 females with ages ranging from 15 to 50 years and refractive error of not more than + 4D.
The mean intraocular pressure was 16.04 with SD 2.71. There were 3 eyes showing intraocular pressure of 20 mm Hg or more. The mean rise of tension after 6 weeks of treatment was 2.88 mm Hg. 22% of the eyes showed a rise of 6 mm or above [Table - 1]. Maximum response was obtained in low myopes where 12 out of 25 (48%) showed a rise in tension of 6 mm Hg or more [Table - 2].
Discussion | | |
The mean intraocular pressure of 16.24 mm Hg in high myopes is higher than the mean intraocular pressure reported in emmetiopes by various authors from time to time (GOLDMAN et al [10] 15.45; LEVENE [15] 14.7; GILL et al [9] 14.9). The higher mean intraocular pressure in the control series of 16.04 mm Hg can be explained due to the presence of excess of low myopes.
Seven out of 17 subjects in whom medicine was used in one eye only, showed contralateral response in the untreated eyes. All these cases fell into responders group. This rise in tension had been explained on the basis of systemic absorption of potent drug influencing a steroid sensitive contralateral eye.[2],[18] Such a high absorption is not likely to occur as period of application is too short to cause this effect. - Systemic administration of drug have been known to cause rise of tension in the eyes but the period required had been more than a year. [11],[14] Such a consensual response has been known to occur after a variety of injuries including chemical, mechanical, thermal and anaphylactic; after administration of pilocarpine or concussion injury to one eye. [19] The prevention of this effect by systemic atropine suggests it to be a parasympathetic effect.[17] Some such mechanism may be operable in the case of steroids also. Such a contralateral response questions the advisability of using one eye as a control in various experiments on human volunteers. Motivation of a subject and ensuring drug application to one eye only had been quite difficult in the present series. We believe that it is desirable to use the drug in both eyes to ensure reliability of drug application and avoid contralateral response.
We have used the magnitude of rise in intraocular pressure as suggested by Armaly [1] for classification of three levels of response. The classification of response on the basis of intraocular pressure attained as advocated by BECKER[5] would have placed all the 9 eyes showing an intraocular pressure of 20 mm Hg and above in the responder group even without a rise of intraocular pressure after steroid treatment. Also those eyes showing intraocular pressure near 20 mm Hg would have needed a small rise to be placed in the responder group. This would have resulted in 10-20%more responders.
There was a larger number of responders in the high myopes as compared to control group in this series or normal population by other authors [Table - 1]. This higher response and higher mean intraocular pressure in high myopes than in the normal population could mean a higher prevalence of chronic simple glaucoma in high myopes. The higher prevalence of responders in low myopes as compared to emmetropes and hypermetropes could mean a higher prevalence of responders in myopes as a whole. Various factors such as age, presence of diabetes and diabetic retinopathy, chronic simple glaucoma, family history of glaucoma have been suggested to influence steroid response. Myopia is another factor which influences the steroid response to a great extent.
Raised intraocular pressure has been blamed by several authors to cause stretching of the eye ball leading to progressive myopia. DIAZ [7] suggested that raised intraocular pressure might be due to degenerative changes in the filtration angle of high myopes. Later DIAZ [8] suggested that the two entities of open angle glaucoma and degenerative myopia might be genetically associated and transmitted by separate or allied gene located together on the same chromosome. This study has revealed a very high percentage of responders (89%) in high myopes showing degenerative changes in the eye. If we are to believe the genetic theory of steroid response, a significant association between glaucoma gene and myopic gene responsible for degenerative changes is clearly established.
The state of intraocular pressure and proneness to increased intraocular pressure in high myopia ought to be seriously thought of in the etiopathogenesis of progressive myopia besides other environmental and biological factors implicated by many authors. The steroid provocative test may also be of value to detect chronic simple glaucoma in high myopes where sometimes it is difficult to confirm it by study of visual field and appearance of optic disc which are equally affected by both conditions.
Summary | | |
The response of intraocular pressure to topical steroids administered four times a day for 6 weeks, to 50 subjects of high myopia comprising 77 eyes and 30 subjects of refractive error of ± 4 D comprising 50 eyes was studied. A significantly high prevalence of responders in high myopes was found. A genetic relationship between chronic simple glaucoma and myopia is suggested. The low myopes in the control group showed a significantly higher prevalence of responders than emmetropes and hypermetropes. Myopic refractive error affects the steroid response to a large extent.
References | | |
1. | Armaly, M. F.: Statistical attributes of the steroid hypertensive response in the clinically normal eye, I. The demonstration of three levels of response. Invest. Ophth. 4: 187, 1965. |
2. | Armaly, M. F.: The heritable nature of dexamethasone induced ocular hypertension. Arch. Ophth. (Chicago) 75: 32, 1966. |
3. | Armaly, M. F.: Inheritance of dexamethasone hypertension and glaucoma. Arch. Ophth. (Chicago) 77: 747, 1967. |
4. | Becker, B. and Hahn, K. A.: Topical corticosteroids and heredity in primary open angle glaucoma. Amer. J. Ophth. 57: 543, 1964. |
5. | Becker, B., Bresnick, G., Chevrette, L.; Kolkar, A. E.; Oaks, C. & Cibis, A.: Intraocular pressure and its response to topical corticosteroid in diabetes. Arch. Ophth. (Chicago) 76: 477, 1966. |
6. | Cristiansson, J.: Glaucoma simplex in diabetes mellitus. Acta Ophth. 43: 224, 1963. |
7. | Diaz, D. D.: Quoted by Podos, et al (1966). |
8. | Diaz, D. D.: Abstr. Excerpta Medica Ophth. 21: 112 (962), 1967. |
9. | Gill, M. M. S.; Jain, I. S.: Ocular changes in young diabetics had their response to intraocular pressure to topical steroids. Paper presented to All India Ophthalmological Society, (1969). |
10. | Goldman, H.: Applanation tonometry, glaucoma. Transaction of second conference, New York: Jasiah Macy Jr. Foundation. (1957). |
11. | Havland, K. R. and Ellis, P. P.: Ocular changes in renal transplant patients. Amer. J. Ophth. 63: 283, 1967. |
12. | Jain, I. S.; Luthra, C. L. and Das, T.: Beneficial effect of myopia on diabetic retinopathy J. All Ind. Ophth. Soc; 13: 88, 1965. |
13. | Jain, I. S. and Luthra, C. L.: Diabetic retinopathy and its relationship with intraocular pressure. Arch. Ophth. (Chicago) 78: 198, 1967. |
14. | Lee, P. F.: The influence of systemic steroid therapy on the intraocular pressure. Amer. J. Ophth. 46: 328, 1956. |
15. | Levene, R.: Tonometry and tonography in group health population. Arch. Ophth. (Chicago) 66: 42, 1961. |
16. | Podos, S. M.; Becker, B. and Morten, W.: High myopia and primary open angle glaucoma. Amer. J. Ophth. 62: 1039, 1966. |
17. | Prijot, E. L. and Stone, H. H.: On the ophthalmic consensual reaction and its relationship to aqueous humor dynamics. Amer. J. Ophth. 42: 500, 1956. |
18. | Schwartz, B.: The response of ocular pressure to corticosteroids. In Int. Ophth. Cl 6: 4: Boston, Little Brown, p. 929, 1966. |
19. | Willet, G. S.: Autonomic effector drugs and normal human eye. Amer. J. Ophth., 68: 216, 1969. |
[Figure - 1], [Figure - 2]
[Table - 1], [Table - 2]
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