Korean J Ophthalmol.  2007 Mar;21(1):28-32. 10.3341/kjo.2007.21.1.28.

The Therapeutic Effects of Angiotensin-Converting Enzyme Inhibitors in Severe Non-proliferative Diabetic Retinopathy

• Cha YJ
• Kim SJ

• KMID: 1105027
• DOI: http://doi.org/10.3341/kjo.2007.21.1.28

Abstract

PURPOSE: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACE-I) in retarding progression of severe non-proliferative diabetic retinopathy (NPDR) in normotensive type 2 diabetic patients. METHODS: This was a retrospective case control study of 128 patients with normotensive type 2 diabetes with lower than +1 dipstick proteinuria and severe NPDR who were classified into either an ACE-I treated group (Enalapril maleate 10 mg, n=12 , Ramipril 5 mg, n=17) or an ACE-I untreated group (n=99). Medical records were reviewed for endpoints of (a) occurrence of proliferative diabetic retinopathy (PDR) or macular edema (ME) for which laser phototherapy was necessary or (b) development of proteinuria of higher than +1 level requiring medication of ACE-I. RESULTS: From the total of 128 patients, there were 29 ACE-I treated patients and 99 ACE-I untreated patients. There were no differences in the average age, duration of diabetes, body mass indices, blood pressure and levels of hyperglycemia or HbA1C between the two groups. Blood pressure and HbA1C levels in both groups remained unchanged during the study. The mean follow-up period was 41.6 months. In the ACE-I group, 6 patients progressed to PDR, 5 to ME and 6 developed proteinuria of greater than +1 over the follow-up period. In the control group, 30 patients progressed to PDR, 6 to ME and 9 developed proteinuria of greater than +1 over the follow-up period. CONCLUSIONS: Small doses of ACE-I did not yield any beneficial effects in retarding the progression of severe NPDR.

Keyword

ACE inhibitor (ACE-I); Non-proliferative Diabetic Retinopathy (NPDR); Proteinuria

MeSH Terms

Treatment Failure
Severity of Illness Index
Retrospective Studies
Ramipril/administration & dosage/*therapeutic use
Middle Aged
Male
Humans
Fundus Oculi
Female
Enalapril/administration & dosage/*therapeutic use
Dose-Response Relationship, Drug
Disease Progression
Diabetic Retinopathy/*drug therapy/pathology
Diabetes Mellitus, Type 2
Case-Control Studies
Angiotensin-Converting Enzyme Inhibitors/administration & dosage/*therapeutic use
Aged

Figure

• 

  Fig. 1 Patients reaching study endpoints. *Group 1 : ACE-I treated group. †PDR : proliferative diabetic retinopathy. ‡ME : macular edema. §PRO : ≥ 1+ Proteinuria. ΠGroup 2 : Control group (ACE-I untreated).

Reference

1. Porta M, Allione A. Current approaches and perspectives in the medical treatment of diabetic retinopathy. Pharmacol Ther. 2004. 103:167–177.

2. Cohen RA, Hennekens CH, Christen WG, et al. Determinants of retinopathy progression in type 1 diabetes mellitus. Am J Med. 1999. 107:45–51.

3. Klein R, Klein BEK. . Vision disorders in diabetes. Diabetes in America. 1995. 2nd ed. Washington DC: NIH Publication;chap. 14.

4. Aiello L, Cavallerano J, Brusell SE. Diabetic eye disease. Endocrinol Metabol Clin North Am. 1996. 25:271–292.

5. Funatsu H, Yamashita H. Pathogenesis of diabetic retinopathy and the renin-angiotensine system. Ophthalmic Physiol Opt. 2003. 23:495–501.

6. Danser AHJ, van den Dorpel MA, Deinum J, et al. Renin, prorenin, and immunoreactive renin in vitreous fluid from eyes with and without diabetic retinopathy. J Clin Endocrinol Metab. 1989. 68:160–167.

7. Danser AHJ, Derkx FHM, Admiraal PJJ, et al. Angiotensin levels in the eye. Invest Ophthalmol Vis Sci. 1994. 35:1008–1018.

8. Funatsu H, Yamashita H, Nakanishi Y, et al. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with proliferative diabetic retinopathy. Br J Ophthalmol. 2002. 86:311–315.

9. Funatsu H, Yamashita H, Ikeda T, et al. Angiotensin II and vascular endothelial growth factor in the vitreous fluid of patients with diabetic macular edema and other retinal disorders. Am J Ophthalmol. 2002. 133:537–543.

10. Wagner J, Danser AHJ, Derkx FHM, et al. Demonstration of renin mRNA, angiotensinogen mRNA, and angiotensin converting enzyme mRNA expression in the human eye: evidence for an intraocular renin-angiotensin system. Br J Ophthalmol. 1996. 80:159–163.

11. Park WC, Han YB. Relationship of diabetic retinopathy and serum angiotensin-converting enzyme. J Korean Ophthalmol Soc. 1988. 29:847–850.

12. Parving HH, Larsen M, Hommel E, et al. Effect of antihypertnensive treatment on blood-retinal permeability to fluorescein in hypertnesive type 1 (insulin-dependent) diabetes patients with background retinopathy. Diabetologia. 1989. 32:440–444.

13. Le Noble FA, Hekking JW, Van Straaten HW, et al. Angiotensin II stimulates angiogenesis in the chorioallantoic membrane of the chick embryo. Eur J Pharmacol. 1991. 195:305–306.

14. Chaturvedi N, Sjolie AK, Stephenson JM, et al. (the EUCLID Study Group). Effect of lisinopril on progression of retinopathy in normotensive people with type 1 diabetes. Lancet. 1998. 351:28–31.

15. Early Treatment Diabetic Retinopathy Study (ETDRS) Research Group. Grading diabetic retinopathy from stereoscopic color fundus photographs-an extension of the modified Arlie House Classification (ETDRS Report Number 10). Ophthalmology. 1991. 98:786–806.

16. Heum C, et al. Diabetes mellitus and the eye. Seoul national university book. 2000. 1st ed. 145–149.

17. Aiello LP, Cahill MT, Wong JS. Systemic considerations in the management of diabetic retinopathy. Am J Ophthalmol. 2001. 132:760–776.

18. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. N Eng J Med. 2000. 342:381–389.

19. Jackson E, Holmes D, Garg S, et al. Angiotensin-converting enzyme inhibitor therapy and diabetic retinopathy. Ann Ophthalmol. 1992. 24:99–103.

20. Rachmani R, Lidar M, Levy Z, et al. Effect of enalapril on the incidence of retinopathy in normotensive patients with type 2 diabetes. Eur J Intern Med. 2000. 11:48–50.

21. Pradhan R, Fong D, March C, et al. Angiotensin-converting enzyme inhibition for the treatment of moderate to severe diabetic retinopathy in normotensive type 2 diabetic patients. A pilot study. J Diabetes Complications. 2002. 16:377–381.

22. Orchard TJ, Forest KYZ, Ellis D, et al. Cumulative glycemic exposure and microvascular complications in insulin-dependent diabetes mellitus. Arch Intern Med. 1997. 157:1851–1856.