Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 Jan 31:1:CD006127.
doi: 10.1002/14651858.CD006127.pub2.

Blood pressure control for diabetic retinopathy

Diana V Do  1 , Xue Wang, Satyanarayana S Vedula, Michael Marrone, Gina Sleilati, Barbara S Hawkins, Robert N Frank
Affiliations
Meta-Analysis

Blood pressure control for diabetic retinopathy

Diana V Do et al. Cochrane Database Syst Rev. .

Update in

  • Blood pressure control for diabetic retinopathy.
    Do DV, Han G, Abariga SA, Sleilati G, Vedula SS, Hawkins BS. Do DV, et al. Cochrane Database Syst Rev. 2023 Mar 28;3(3):CD006127. doi: 10.1002/14651858.CD006127.pub3. Cochrane Database Syst Rev. 2023. PMID: 36975019 Free PMC article.

Abstract

Background: Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure.

Objectives: The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti-hypertensive medications with respect to the same outcomes.

Search methods: We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data.

Selection criteria: We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti-hypertensive agents versus placebo.

Data collection and analysis: Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost-effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials.

Main results: We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti-hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government-sponsored grants and institutional support.Study designs, populations, interventions, and lengths of follow-up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants.For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow-up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4- to 5-year follow-up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review.The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4- to 5-year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4- to 5-year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best-corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow-up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings.The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials.

Authors' conclusions: Hypertension is a well-known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy.

PubMed Disclaimer

Conflict of interest statement

DECLARATIONS OF INTEREST

The authors have no conflicts to declare.

Figures

Analysis 1.1
Analysis 1.1
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 1 Incidence of retinopathy at 4 to 5 years.
Analysis 1.2
Analysis 1.2
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 2 Progression of retinopathy at 4 to 5 years.
Analysis 1.3
Analysis 1.3
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 3 Combined incidence and progression of DR, 4 to 5 years.
Analysis 1.4
Analysis 1.4
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 4 Incidence of PDR/CSME at 4 to 5 years.
Analysis 1.5
Analysis 1.5
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 5 Visual acuity (loss of 3 lines or more), 4 to 5 years in type 2 diabetics.
Analysis 1.6
Analysis 1.6
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 6 Adverse events - All cause mortality.
Analysis 1.7
Analysis 1.7
Comparison 1 Blood pressure control versus no (or less) control by type of diabetes, 4 to 5 years, Outcome 7 Adverse events - Hypotension.
Analysis 2.1
Analysis 2.1
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 1 Incidence of DR at 4 to 5 years.
Analysis 2.2
Analysis 2.2
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 2 Progression of DR, 4 to 5 years.
Analysis 2.3
Analysis 2.3
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 3 Combined incidence and progression of DR, 4 to 5 years.
Analysis 2.4
Analysis 2.4
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 4 Incidence of PDR/CSME at 4 to 5 years.
Analysis 2.5
Analysis 2.5
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 5 Visual acuity (loss of 3 lines or more), 4 to 5 years.
Analysis 2.6
Analysis 2.6
Comparison 2 Blood pressure control versus no (or less) control by type of hypertension, 4 to 5 years, Outcome 6 Adverse events - All cause mortality.
Analysis 3.1
Analysis 3.1
Comparison 3 Blood pressure control versus no (or less) control by type of diabetes, 1 to 2 years, Outcome 1 Incidence of DR, 1.5 to 2 years.
Analysis 3.2
Analysis 3.2
Comparison 3 Blood pressure control versus no (or less) control by type of diabetes, 1 to 2 years, Outcome 2 Progression of DR, 1.5 to 2 years.
Analysis 3.3
Analysis 3.3
Comparison 3 Blood pressure control versus no (or less) control by type of diabetes, 1 to 2 years, Outcome 3 Combined incidence and progression of DR, 1.5 to 2 years.
Analysis 3.4
Analysis 3.4
Comparison 3 Blood pressure control versus no (or less) control by type of diabetes, 1 to 2 years, Outcome 4 Incidence of PDR, 1.5 to 2 years, Type 1 diabetes.
Figure 1
Figure 1
Results of searching for studies for inclusion in the review
Figure 2
Figure 2
Risk of bias summary: review authors’ judgements about each risk of bias item for each included study. Missing cells indicate that study did not measure corresponding review outcomes.
See this image and copyright information in PMC

Comment in

  • Blood pressure control for diabetic retinopathy.
    Do DV, Wang X, Vedula SS, Marrone M, Sleilati G, Hawkins BS, Frank RN. Do DV, et al. Sao Paulo Med J. 2015 May-Jun;133(3):278-9. doi: 10.1590/1516-3180.20151333T1. Epub 2015 Jun 1. Sao Paulo Med J. 2015. PMID: 26176931 Free PMC article.

References

References to studies included in this review

    1. Schrier RW, Estacio RO, Esler A, Mehler P. Effects of aggressive blood pressure control z in normotensive type 2 diabetic patients on albuminuria, retinopathy and strokes. Kidney International. 2002;61(3):1086–97. - PubMed
    2. Schrier RW, Estacio RO, Jeffers B. Appropriate Blood Pressure Control in NIDDM (ABCD) Trial. Diabetologia. 1996;39(12):1646–54. - PubMed
    3. Schrier RW, Savage S. Appropriate Blood Pressure Control in Type II Diabetes (ABCD Trial): implications for complications. American Journal of Kidney Diseases. 1992;20(6):653–7. - PubMed
    1. Estacio RO, Jeffers BW, Gifford N, Schrier RW. Effect of blood pressure control on diabetic microvascular complications in patients with hypertension and type 2 diabetes. Diabetes Care. 2000;23(Suppl 2):B54–64. - PubMed
    2. Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin dependent diabetes and hypertension. The New England Journal of Medicine. 1998;338(10):645–52. - PubMed
    3. Savage S, Nagel NJ, Estacio RO, Feig PU, MacCarthy EP, Lukken NJ, et al. The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial. Rationale and design of a trial of hypertension control (moderate or intensive) in type II diabetes. Online Journal of Current Clinical Trials. 1993 Nov 24; Doc No 104. - PubMed
    1. Ambrosius WT, Danis RP, Goff DC, Jr, Greven CM, Gerstein HC, Cohen RM, et al. Lack of association between thiazolidinediones and macular edema in type 2 diabetes: the ACCORD eye substudy. Archives of Ophthalmology. 2010;128(3):312–8. - PMC - PubMed
    2. Buse JB, Bigger JT, Byington RP, Cooper LS, Cushman WC, Friedewald WT, et al. Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial: design and methods. American Journal of Cardiology. 2007;99(12A):21i–33i. - PubMed
    3. Chew EY, Ambrosius WT. Update of the ACCORD Eye Study. The New England Journal of Medicine. 2011;364(2):188–9. - PubMed
    4. Chew EY, Ambrosius WT, Davis MD, Danis RP, Gangaputra S, Greven CM, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. The New England Journal of Medicine. 2010;363(3):233–44. - PMC - PubMed
    5. Chew EY, Ambrosius WT, Howard LT, Greven CM, Johnson S, Danis RP, et al. Rationale, design, and methods of the Action to Control Cardiovascular Risk in Diabetes Eye Study (ACCORD-EYE) American Journal of Cardiology. 2007;99(12A):103i–11i. - PubMed
    6. Cushman WC, Grimm RH, Cutler JA, Evan GW, Capes S, Corson MA. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. American Journal of Cardiology. 2007;99(12A):44i–55i. - PubMed
    7. Ismail-Beigi F, Craven T, Banerji MA, Basile J, Calles J, Cohen RM, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet. 2010;376(9739):419–30. - PMC - PubMed
    8. Ismail-Beigi F, Craven TE, O’Connor PJ, Karl D, Calles-Escandon J, Hramiak I, et al. Combined intensive blood pressure and glycemic control does not produce an additive benefit on microvascular outcomes in type 2 diabetic patients. Kidney International. 2012;81(6):586–94. - PMC - PubMed
    9. Sullivan MD, Anderson RT, Aron D, Atkinson HH, Bastien A, Chen J, et al. Health-related quality of life and cost-effectiveness components of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: rationale and design. American Journal of Cardiology. 2007;99(12A):90i–102i. - PubMed
    1. ADVANCE Collaborative Group. ADVANCE - Action in Diabetes and Vascular Disease: patient recruitment and characteristics of the study population at baseline. Diabetic Medicine. 2005;22(7):882–8. - PubMed
    2. ADVANCE Collaborative Group. Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial. Lancet. 2007;370(9590):829–40. - PubMed
    3. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. The New England Journal of Medicine. 2008;358(24):2560–72. - PubMed
    4. ADVANCE Management Committee. Study rationale and design of ADVANCE: Action in Diabetes and Vascular Disease - preterax and diamicron MR controlled evaluation. Diabetologia. 2001;44(9):1118–20. - PubMed
    5. Beulens JWJ, Patel A, Vingerling JR, Cruickshank JK, Hughes AD, Stanton A, et al. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomized controlled trial. Diabetologia. 2009;52(10):2027–46. - PubMed
    6. Patel A, Chalmers J, Neal B, Chapman N, Girgis S, MacMahon S. Blood pressure lowering in diabetes: a brief review of current evidence and description of a new trial. Clinical and Experimental Pharmacology and Physiology. 2001;28(12):1108–11. - PubMed
    7. Poulter NR. Blood pressure and glucose control in subject with diabetes: new analysis from ADVANCE. Journal of Hypertension. 2009;27(1):S3–8. - PubMed
    8. Stolk RP, Vingerling JR, Cruickshank JK, Hughes AD, Stanton A, Juming L, et al. Rationale and design of the AdRem study: evaluating the effects of blood pressure lowering and intensive glucose control on vascular retinal disorders in patients with type 2 diabetes mellitus. Contemporary Clinical Trials. 2007;28(1):6–17. - PubMed
    9. Stolk RP, van Schooneveld MJ, Cruickshank JK, Hughes AD, Stanton A, Lu J, et al. Retinal vascular lesions in patients of Caucasian and Asian origin with type 2 diabetes: baseline results from the ADVANCE Retinal Measurements (AdRem) study. Diabetes Care. 2008;31(4):708–13. - PubMed
    1. BENEDICT Group. The BErgamo NEphrologic DIabetes Complications Trial (BENEDICT) Controlled Clinical Trials. 2003;24(4):442–61. - PubMed
    2. Ruggenenti P, Fassi A, Parvanova I, Bruno S, Iliev IP, Brusegan V, et al. Preventing microalbuminuria in type 2 diabetes. The New England Journal of Medicine. 2004;351(19):1941–51. - PubMed
    3. Ruggenenti P, Iliev I, Filipponi M, Tadini S, Perna A, Ganeva M. Effect of trandolapril on regression of retinopathy in hypertensive patients with type 2 diabetes: a prespecified analysis of the benedict trial. Journal of Ophthalmology. 2010;2010 Article ID 106384. - PMC - PubMed

References to studies excluded from this review

    1. Araki A, Iimuro S, Sakurai T, Umegaki H, Iijima K, Nakano H, et al. Long-term multiple risk factor interventions in Japanese elderly diabetic patients: the Japanese Elderly Diabetes Intervention Trial-study design, baseline characteristics and effects of intervention. Geriatrics and Gerontology International. 2012;12(Suppl 1):7–17. - PubMed
    1. Auyanet I, Rodriguez LJ, Esparza N, Cabrera F, Rossique P, Suria S, et al. Does carvedilol minimize the requirements for laser photocoagulation in diabetic retinopathy? [Minimiza el carvedilol los requerimientos de fotocoagulacion laser en la retinopatia diabetica?] Nefrologia. 2010;30(issue 4):473–4. - PubMed
    1. Andersen NH, Knudsen ST, Poulsen PL, Poulsen SH, Helleberg K, Eiskjaer H, et al. Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients with diabetes mellitus: rationale and design. Journal of the Renin-Angiotensin-Aldosterone System. 2003;4(2):96–9. - PubMed
    2. Andersen NH, Poulsen PL, Knudsen ST, Poulsen SH, Eiskjaer H, Hansen KW, et al. Long-term dual blockade with candesartan and lisinopril in hypertensive patients with diabetes: the CALM II study. Diabetes Care. 2005;28(2):273–7. - PubMed
    1. Chang CH, Chuang LM. Effects of medical therapies on retinopathy progression in type 2 diabetes: Is blood pressure control the lower the better? Journal of Diabetes Investigation. 2011;2(2):101–3. - PMC - PubMed
    1. Genuth S, Lipps J, Lorenzi G, Nathan DM, Davis MD, Lachin JM, et al. Effect of intensive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA. 2002;287(19):2563–9. - PMC - PubMed
    2. The Diabetes Control and Complications Trial Research Group. Effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. American Journal of Cardiology. 1995;75(14):894–903. - PubMed
    3. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care. 1999;22(1):99–111. - PMC - PubMed

References to studies awaiting assessment

    1. Bedigian M. Improving the prognosis of diabetic patients: evaluating the role of intensive versus moderate blood pressure control with selective angiotensin II receptor block (ARB) therapy. Journal of the Renin-Angiotensin-Aldosterone System. 2000;1(Suppl 2):25–8. - PubMed
    2. Bedigian MP, Estacio RO, Jefferes BW, Biggerstaff S, Schrier RW. Baseline characteristics of the hypertensive cohort of the appropriate blood pressure control in diabetes trial -part 2 with valsartan (ABCD-2V) American Journal of Hypertension. 2000;13(4 Pt 2):56A–7A.
    3. Estacio RO, Coll JR, Tran ZV, Schrier RW. Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes. American Journal of Hypertension. 2006;19(12):1241–8. - PubMed
    4. Shrier RW, Estacio RO, Jeffers BW, Biggerstaff S, Krinsk E, Pincus JR, et al. ABCD-2V: Appropriate blood pressure control in diabetes - part 2 with valsartan. American Journal of Hypertention. 1999;12(4 Pt 2):141A.
    1. Sandbæk A, Griffin SJ, Sharp SJ, Simmons RK, Borch-Johnsen K, Rutten GE, et al. Effect of early multifactorial therapy compared with routine care on microvascular outcomes at 5 years in people with screen-detected diabetes: a randomized controlled trial: The ADDITION-Europe Study. Diabetes Care. 2014;37(7):2015–23. - PubMed
    1. Haller H, Viberti GC, Mimran A, Remuzzi G, Rabelink AJ, Ritz E, et al. Preventing microalbuminuria in patients with diabetes: rationale and design of the Randomised Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) study. Journal of Hypertension. 2006;24(2):403–8. - PubMed

References to ongoing studies

    1. AdDIT Research Group. Adolescent type 1 diabetes cardio-renal intervention trial (AdDIT) BMC Pediatrics. 2009;9:79. - PMC - PubMed
    1. NCT00134160. [accessed 30 July 2013];The study comparing the incidence of cardiovascular events between high-dose ARB monotherapy and combination therapy with ARB and calcium channel blocker in Japanese elderly hypertensive patients at high cardiovascular risk. clinicaltrials.gov/ct2/show/NCT00134160.
    1. NCT00300976. [accessed 30 July 2013];A randomized controlled study of the intensive therapy and the conventional therapy for the suppression of the vascular complications in the type 2 diabetic patients. clinicaltrials.gov/ct2/show/NCT00300976.

Additional references

    1. American Diabetes Association. Diabetic retinopathy. Diabetes Care. 1998;21(1):157–9. - PubMed
    1. Buch H. Prevalence and causes of visual impairment and blindness among Scandinavian adults: the Copenhagen City Eye Study. Ophthalmology. 2004;111(1):53–61. - PubMed
    1. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta (GA): U.S. Department of Health and Human Services, Centers for Disease Control and Prevention; 2011.
    1. Chew E. Association of elevated serum lipid levels with retinal hard exudates in diabetic retinopathy. Early Treatment Diabetic Retinopathy Study (ETDRS) Report 22. Archives of Ophthalmology. 1996;114(9):1079–84. - PubMed
    1. Cushman WC, Grimm RH, Jr, Cutler JA, Evans GW, Capes S, Corson MA, et al. Rationale and design for the blood pressure intervention of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. American Journal of Cardiology. 2007;99(12A):44i–55i. - PubMed

References to other published versions of this review

    1. Sleilati G, Frank RN, Mathew MC. Blood pressure control for diabetic retinopathy. Cochrane Database of Systematic Reviews. 2006;(3) doi: 10.1002/14651858.CD006127. - DOI - PMC - PubMed

Publication types

MeSH terms

Substances