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ORIGINAL ARTICLE |
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Year : 1989 | Volume
: 37
| Issue : 3 | Page : 127-133 |
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Topical sulindac therapy in diabetic senile cataracts : cataract IV
YR Sharma, RB Vajpayee, R Bhatnagar, Madan Mohan, RV Azad, Mukesh Kumar, Ram Nath
Dr. R. P. Centre for Ophthalmic Sciences, All India Institute for Medical Sciences, Ansari Nagar, New Delhi - 110 029, India
Correspondence Address: Y R Sharma Dr. R. P. Centre for Ophthalmic Sciences, All India Institute for Medical Sciences, Ansari Nagar, New Delhi - 110 029 India
Source of Support: None, Conflict of Interest: None | Check |
PMID: 2632448
Sulindac, a non-steroidal anti-inflammatory drug has been found to be a potent inhibitor of enzyme aldose reductase. We used sulindac topically in diabetic senile cataract patients to note if it effects the progression of cataracts. More of sulindac treated eyes maintained initial vision and fewer eyes had visual loss of up to two lines or more as compared to control eyes. The extent and density of different opacities showed less progression in sulindac treated eyes but it was not statistically significant except that the ophthalmoscopically observed density of opacity showed statistically very significant lesser mean increase in sulindac treated eyes. We suggest that sulindac is a potential drug which should be further evaluated in large double blind photodocumented studies in diabetic senile cataracts. Keywords: Sulindac, aldose reductase, dia-betic senile cataracts, prostaglandin pathways
How to cite this article: Sharma Y R, Vajpayee R B, Bhatnagar R, Mohan M, Azad R V, Kumar M, Nath R. Topical sulindac therapy in diabetic senile cataracts : cataract IV. Indian J Ophthalmol 1989;37:127-33 |
Introduction | | |
Senile cataracts are more common in diabetes mellitus, occur earlier and the progression is faster than in the non-diabetic population [1],[2],[3]. Pivotal role of polyol pathway in sugar cataracts in animals has been established and thus inducted cataracts can be slowed down and prevented with the use of aldose reductase inhibitors [4],[5],[6]. The role of the polyol pathway in human diabetic cataracts has been speculated [3]. Elevated sorbitol levels have been reported in human senile cataracts in diabetic patients [7]. Aqueous humour glucose levels are elevated and could possibly exert an osmotic stress through glucose conversion to sorbitol mediated by the enzyme aldose reductase [8]. Elevated blood glucose levels have been reported in non-diabetic senile cataracts. [9] Sulindac, a nonsteroidal antiinflammatory drug, has been described as a potent aldose reductase inhibitor. [10] Sulindacs in vitro and in-vivo efficacy has been demonstrated [11],[12],[13] Sorbinil, another potent aldose reductase inhibitor penetrates the lens after topical application. [14] Indomethacin which like sulindac is a non-steroidal anti-inflammatory drug and belongs to the same group has been recovered from the aqueous humour for upto six hours after topical application. [15] Topical sulindac penetrates the cornea after topical application and is recoverable from the lens. [16] We used topical sulindac in medical treatment of senile cataracts in diabetic population and reported herein are the results.
Material and methods | | |
Patients seen in the cataract cell with known history of diabetes and who consented to participate in the programme were eligible to enter the study. Most of these patients were controlled by diet and oral anti-diabetic agents; few were also on insulin treatment. Control of diabetes was not a factor for inclusion in the study since the contralateral eye was used as control. Patients who had diabetic retinopathy of any grade were excluded. The eye judged to have more advanced cataract was put on topical 1 percent sulindac drops qid and placebo drops were prescribed qid for the fellow eye. Sulindac was dissolved in phosphate buffer 0.05M, Ph 8.00. Because sulindac drops were yellow in colour and placebo drops were colourless the vials used were not labeled. The patient was asked to use the "yellow" eye drops in eye having more advanced cataract and colourless drops for fellow eye. The methodology and examination procedures have been described previously. [17],[18],[19] Patients were followed up at one month intervals and initially a follow up of two years was planned. 50 patients were included in the study.
Results | | |
Large drop out rate encountered in our studies on medical therapy of cataract was even more marked in the diabetic group. Of fifty patients, none completed even one year's follow up. Maximum follow up obtained was 9 months. Only 21 out of 50 patients completed a follow up of at least 3 months (5.42+2.01, m+SD). Data on 21 patients who were followed up for 3 months or more was analysed [Table - 1]. Very few patients had pure cataracts. Most were of the mixed type. The distribution of cortical and PSC opacities was similar in both group of eyes initially and at final follow up, but in control eyes 11(52.38%) had nuclear cataracts initially and at completion of follow up 16 eyes (76.19%) had them while in sulindac treated eyes, the number of nuclear cataracts remained same (16=76.19%; [Table - 2] p 0.05).
Of 21 control eyes, only 2 maintained the same vision while in sulindac treated eyes 13 of 21 eyes maintained the same vision (P< 0.002; [Table - 3]). Loss of upto 2 lines or more occurred in 19 of 21 control eyes - in sulindac group 7 eyes had loss of upto 2 lines and only 1 had loss of upto 4 lines (P < 0.05). The same trend was observed in mean percentage acuity loss during follow up. In control group, mean increase of percentage acuity loss was 24.51; in sulindac treated eyes as compared to control eyes but the difference was not statistically significant (P>0.05; Tale 5 and [Table - 6]). The increase in nuclear opacity density showed no difference in the two groups but mean increase in extent of nuclear opacity was greater in control eyes as compared to sulindac treated eyes but again difference was not statistically significant (P > 0.05; [Table - 7] & [Table - 8]). The difference in mean increase in extent of density of PSC was also not statistically significant though the mean increase in PSC density was greater in sulindac treated eyes. (P > 0.05; [Table - 9][Table - 10]. The mean increase in ophthalmoscopically observed opacity was similar in two groups but ophthalmoscopically observed density showed a considerably greater increase in control eyes (P < 0.05; [Table - 11][Table - 12].
No ocular side effects were noted during the follow up in both groups.
Discussion | | |
The study with topical sulindac drops in senile cataracts in diabetics was marked with a very considerable drop out rate which was even more marked than in the glutathione group. [18] None of the 50 patients put on topical sulindac completed the planned two years follow up. Maximum follow up obtained was nine months and only 21 patients completed follow up of at last three months. Perhaps greater preoccupation with the diabetic state accounts for this. The visual status remained better in sulindac treated eyes. a significantly greater number of sulindac treated eyes maintained the initial vision. 19 eyes in the control group had loss of upto two lines or more while in sulindac group only 8 eyes had loss of upto 2 lines or more. Only 2 control eyes maintained the initial vision. The percentage distribution of cortical and PSC opacities was similar in the two groups, but no eye on sulindac developed nuclear opacity denova. This happened in five eyes in control group. Mean increase in percentage visual acuity loss was considerably more in control eyes ( p< 0.05)
Except for nuclear density and PSC opacity extent which showed similar mean increase in two groups, the extent and density of slit lamp observed sub-types of opacities showed greater mean increase in control eyes but in case was it statistically significant (p> 0.05). Interestingly ophthalmoscopically observed extent of opacity showed approximately similar mean increase bu t sulindac treated eyes showed very significant less mean increase in ophthalmoscopically observed opacity density (p < 0.005).
In conclusion, our data based on limited number of patients and limited follow up indicates that sulindac maybe potentially useful in senile cataracts in diabetics. To establish this, and before any such recommendation can be made, it is most imperative that double blind large scale photo-documented studies be undertaken. The beneficial role of sulindac in senile cataracts in diabetics could be ascribed besides aldose reductase inhibition to inhibition of the enzymes of the prostaglandin pathway 20 and its membrane stabilising properties."' The reversibility of retinal capillary leakage in early diabetic retinopathy by use of systemic sulindac has been reported.[22] Sulindac is the only potent aldose reductase inhibitor which is currently clinical use.
Acknowledgement | | |
We thank Dr. D.E. Duggan of Merck Sharp and Dohme, West Point, Philadelphia for kindly supplying us Sulindac. We gratefully acknowledge, our thanks to ICMR India for partly supporting this study. During part of this study, Dr. Y.R. Sharma was appointed under the supernumerary research cadre scheme at Dr. R.P. Centre. We thank all the residents who referred their cases to the cataract cell[22].
References | | |
1. | Caird Fl,Hutchinson M,Pirie A.Cataract and Diabsetes. Br Med 1 1964; 12:665-668. |
2. | Ederer F, Hitler R, Taylor HR. Senile lens changes and diabetes in two population studies. Am J Ophthalmol 1981; 91:361-395. |
3. | Caird Fl, Pine A, Rarrasell TG. Diabetes and the eye. Oxford and Edinburgh. Blackwell Scientific Publications, 1969. |
4. | Kinoshita JH. Mechanisms initiating catarct formation. Invest ophthaimol vis Sci 1974; 13: 713-724. |
5. | Kinoshita JH, Kador P, Datiles M. Aldose reductase in diabetic cataracts. JAMA 1981; 246:257-261 |
6. | Kador PF, Kinoshita JH. Diabetic and galactosemic cataracts. In: Regnault F'J. Sci Adv. Symposium on the lens. Amsterdam Excerpta Medica, 19:110-123. |
7. | Varma SD, Schocket SS, Richards RD. Implications of aldose reductose in cataracts in human diabetes. invest Ophthalmol vis scl 1979,18:237-242. |
8. | Davies PD< Duncan G, Pynsent PB, Arber DL, Lucas VA. Aqueous humour glucose concentration in caract patients and the effect on the lens. Exp eye res 1984, 39: 605-609. |
9. | Dugmore LVI, Gun K. Glucose. tolerance test in 200 patients with senile cataracts; Dr. J Ophthalmol 1980, 64:689-692. |
10. | Sharma YR, Cotlier E. Inhibition of lens and ctaract aldose reductase by protein bound anti-rheumatic drugs: Salicylate, Indomethacin, Oxyphenbutazone, Sulindac. Exp eye res 1982, 35:21-27. |
11. | Jacobson M, Sharma YR, Cotlier E, Hollander JD. Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil : Two novel aldose reductase inhibitors. Invest ophthalmot vis sci 1983, 24:1426-1429. |
12. | Sharma YR, Richards RD, Varma SD. Sugar cataracts in gerbil. Effect of quercetin, Sulindac and sulindac sulfide. ARVO abstracts. Invest ophthalmI Vis Sci 1983 : 263. |
13. | Sharma YR, Bhatnagar R, Vajpayee RB, Azad RV, and Mukesh Kumar. The effectivity of sulindac in sugar cataracts. Devel Ophthalmol, In Press. |
14. | Crabbe MJC, Petachey M, Burgess SEP, Cheng H> The penetration of sorbinil, an aldpse reductase inlibitor into lens, Aqueous humour and enyhrocytes of patients undergoing cataracts extraction. Exp Eye Res 1985, 40: 95-99, |
15. | Hanna C, Sharp JD, Rock L. Ocular absorption of indomethacin by the rabbit. arch ophthalmol 1972, 88:196-198. |
16. | Duggan DE, personal communication 1983. |
17. | Sharma YR, Vaipayee RB, Madan Mohan, Azad RV, Mukesh Kumar. A simple accurate method of cataract classification Cataract 1. Manuscript submitted for publication. |
18. | Ibid. Methodology for studies on medical therapyof cataracts : cataract II. Manuscript submitted for publication. |
19. | Ibid. Topical glutathiotlein therapy in sensile cataract: Cataract III. Manuscript submitted for publication. |
20. | Frank RN. The mechanism of blood retinal carrier breakdown in diabetes. Arch Ophthalmol 1985: 103:1303-1304. |
21. | Mizushima Y. Sakai S, Yamamura M. Mode of stabilising action of non-steroid anti-inflammatory drugs on erythrocycle membrane. Biochem Phermacol 1976; 19:227-234. |
22. | Cunah-Vaz JG, Mota CC, Leite EC et al. Effect of sulindac on permeability of the blood retinal barriers in early diabeticrationapthy. ArchOphthalmol1985; 10: 1307-1311. |
[Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5], [Table - 6], [Table - 7], [Table - 8], [Table - 9], [Table - 10], [Table - 11], [Table - 12]
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