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Effects of aldose reductase inhibition with tolrestat on diabetic retinopathy in a six months double blind trial

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Abstract

To study the effects of the new aldose reductase inhibitor tolrestat on diabetic retinopathy, 31 diabetic patients with various degrees of retinopathy were randomly assigned to either tolrestat (200 mg once daily) or placebo treatment for six months. Separate morphological features of diabetic retinopathy were assessed by fundus photography and fluorescein angiography before and at the end of the study. The results showed some amelioration of clinical signs of diabetic retinopathy during aldose reductase treatment. Hard exudates, intraretinal hemorrhages and focal fluorescein leakage increased on average in the placebo and decreased in the tolrestat group. The difference was statistically significant for focal fluorescein leakage only. The permeability of the blood retinal barrier was determined by vitreous fluorophotometry before and at the end of the study. No change in permeability values was found.

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References

  1. Kinoshita JH, Nishimura C. The involvement of aldose reductase in diabetic complications. Diab Metab Rev 1988; 4: 649–56.

    Google Scholar 

  2. Kador PF. The role of aldose reductase in the development of diabetic complications. Med Res Rev; 1988: 325–52.

  3. Hotta N, Katuta H, Fukasawa H, et al. Prevention of diabetic retinopathy by aldose reductase inhibitor in fructose-fed streptozotocin-diabetic rat. Diab Res Clin Pract 1985; 1 (suppl): S251.

    Google Scholar 

  4. Engerman RL, Kern TS. Hyperglycemia as a cause of diabetic retinopathy. Metabolism 1986; 35 (suppl): 20–23.

    PubMed  Google Scholar 

  5. Stribling DR, Harrison HE, Gaschen F, et al. Effect of aldose reductase inhibition with Statil (ICI 128436) on retinal capillary basement membrane thickening in streptozotocin diabetic rats. Diabetologia 1986; 29: 597A.

  6. Chakrabarti S, Sima AAF. Pathogenetic heterogeneity in retinal capillary basement membrane thickening in the diabetic BB-rat. Diabetologia 1987; 30: 966–68.

    PubMed  Google Scholar 

  7. Mac Gregor LC, Matschinsky FM. Experimental diabetes mellitus impairs the function of retinal pigmented epithelium. Metabolism 1986; 35 (suppl): 28–34.

    PubMed  Google Scholar 

  8. Funada M, Okamoto I, Fujinaga Y, et al. Effects of aldose reductase inhibitor (M79175) on ERG oscillatory potential abnormalities in streptozotocin-induced diabetes in rats. Jpn J Ophthalmol 1987; 31: 305–14.

    PubMed  Google Scholar 

  9. Segawa M, Hirata Y, Fuijimori S, et al. The development of electroretinogram abnormalities and the possible role of polyol pathway activity in diabetic hyperglycemia and galactosemia. Metabolism 1988; 37: 454–60.

    PubMed  Google Scholar 

  10. Blair NP, Tso MOM, Dodge JT. Pathologic studies of the blood-retinal barrier in the spontaneously diabetic BB rat. Invest Ophthalmol Vis Sci 1984; 25: 302–11.

    PubMed  Google Scholar 

  11. Williamson JR, Chang K, Tilton RG, et al. Increased vascular permeability in spontaneously diabetic BB/W rats and in rats with mild versus severe streptozotocin-induced diabetes; prevention by aldose reductase inhibitors and castration. Diabetes 1987; 36: 813–21.

    PubMed  Google Scholar 

  12. Krupin T, Waltman S, Szewczyk P, et al. Fluorometric studies on the blood-retinal barrier in experimental animals. Arch Ophthalmol 1982; 100: 631–34.

    PubMed  Google Scholar 

  13. Srivastava SK, Ansari NH, Hair GA, et al. Activation of human erythrocyte, brain, aorta, muscle and ocular tissue aldose reductase. Metabolism 1986; 35 (suppl): 114–18.

    PubMed  Google Scholar 

  14. Akagi Y, Kador PF, Kuwabara T, et al. Aldose reductase localization in human retinal mural cells. Invest Ophthalmol Vis Sci 1983; 24: 1516–19.

    PubMed  Google Scholar 

  15. Hohman TC, Nishimura C, Robison WG. Aldose reductase in cultured pericytes of human retinal capillaries. Exp Eye Res 1989; 48: 55–60.

    PubMed  Google Scholar 

  16. Akagi Y, Yajima Y, Kador PF, et al. Localization of aldose reductase in the human eye. Diabetes 1984; 33: 562–66.

    PubMed  Google Scholar 

  17. Vinores SA, Campochiaro PA, Williams EH, et al. Aldose reductase expression in human diabetic retina and pigment epithelium. Diabetes 1988; 37: 1658–64.

    PubMed  Google Scholar 

  18. Poulsom R. Inhibition of aldose reductase from human retina. Curr Eye Res 1987; 6: 427–32.

    PubMed  Google Scholar 

  19. Christensen JEJ, Varnek L, Gregersen G. The effect of an aldose reductase inhibitor (sorbinil) on diabetic neuropathy and neural function of the retina: a double blind study. Acta Neurol Scand 1985; 71: 164–67.

    PubMed  Google Scholar 

  20. Muntoni S, Basciu M, Mascia C, et al. Reversal of diabetic dyschromatopsia by pharmacological treatment. Diabetologia 1986; 29: 574A.

    Google Scholar 

  21. Cunha-Vaz JG, Mota CC, Leite EC, et al. Effect of sulindac on the permeability of the blood-retinal barrier in early diabetes. Arch Ophthalmol 1985; 103: 1307–11.

    PubMed  Google Scholar 

  22. Cunha-Vaz JG, Mota CC, Leite EC, et al. Effect of sorbinil on blood-retinal barrier in early diabetic retinopathy. Diabetes 1986; 35: 574–78.

    PubMed  Google Scholar 

  23. Sorbinil Retinopathy Trial Research Group: A randomized trial of sorbinil, an aldose reductase inhibitor, in diabetic retinopathy. Arch Ophthalmol 1990; 108: 1234–44.

    Google Scholar 

  24. Pitts NE, Gundersen K, Mehta DJ, et al. Aldose reductase inhibitors in clinical practice: preliminary studies on diabetic neuropathy and retinopathy. Drugs 1986; 32 (suppl 2): 30–35.

    PubMed  Google Scholar 

  25. Ryder S, Sarokhan B, Shand DG, et al. Human safety profile of tolrestat. Drug Devel Res 1987; 11: 131–43.

    Google Scholar 

  26. The Diabetic Retinopathy Study Research Group. Report 7. A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 1981; 21: 210–26.

    Google Scholar 

  27. van Gerven JMA, Boot JP, Lemkes HHPJ, van Best JA. Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy. Doc Ophthalmol 1992; 80: 183–88.

    PubMed  Google Scholar 

  28. Boot JP, van Best JA, Tjin A Tsoi EWSJ, et al. Plasma fluorescein decay determination during fluorophotometry. Doc Ophthalmol 1987; 65: 403–22.

    PubMed  Google Scholar 

  29. Kappelhof JP, van Best JA, van Valenberg PLJ, et al. Inward permeability of the bloodretinal barrier by fluorophotometry. Invest Ophthalmol Vis Sci 1987; 28: 665–71.

    PubMed  Google Scholar 

  30. van Best JA, Kappelhof JP, Laterveer L, Oosterhuis JA. Blood aqueous barrier permeability versus age by fluorophotometry. Curr Eye Res 1987; 6: 855–63.

    PubMed  Google Scholar 

  31. van Best JA, Bollemeijer JG, Sterk CC. Corneal transmission in whole human eyes. Exp Eye Res 1988; 46: 765–83.

    PubMed  Google Scholar 

  32. Weisberg S, Bingham C. Approximate analysis of variance test for non-normality suitable for machine calculation. Technometrics 1975; 17: 133–34.

    Google Scholar 

  33. Davis MD. Diabetic retinopathy: a clinical overview. Diab Metab Rev 1988; 4: 291–22.

    Google Scholar 

  34. Boot JP, van Gerven JMA, van Best JA, et al. Blood retinal and blood aqueous barriers in diabetics by fluorophotometry. Doc Ophthalmol 1989; 71: 19–27.

    PubMed  Google Scholar 

  35. Cunha-Vaz JG, Gray HR, Zeimer RC et al. Characterization of the early stages of diabetic retinopathy by vitreous fluorophotometry. Diabetes 1985; 34: 53–59.

    PubMed  Google Scholar 

  36. The Diabetes Control and Complications Trial Research Group. Color photography vs fluorescein angiography in the detection of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1987; 105: 1344–51.

    Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, The Netherlands

    Joop M. A. Van Gerven & Herman H. P. J. Lemkes

  2. Eye Hospital, Rotterdam, The Netherlands

    Johan P. Boot

  3. Department of Ophthalmology, University Hospital, Rijnsburgerweg 10, 2333 AA, Leiden, The Netherlands

    Jaap A. Van Best

Authors
  1. Joop M. A. Van Gerven
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  2. Johan P. Boot
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  3. Herman H. P. J. Lemkes
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  4. Jaap A. Van Best
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Van Gerven, J.M.A., Boot, J.P., Lemkes, H.H.P.J. et al. Effects of aldose reductase inhibition with tolrestat on diabetic retinopathy in a six months double blind trial. Doc Ophthalmol 87, 355–365 (1994). https://doi.org/10.1007/BF01203344

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  • DOI: https://doi.org/10.1007/BF01203344

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