Retinal Vascular Caliber, Diabetes, and Retinopathy

Retinal Vascular Caliber, Diabetes, and Retinopathy

BRIEF REPORTS Retinal Vascular Caliber, Diabetes, and Retinopathy Annette Kifley, Jie Jin Wang, Sudha Cugati, Tien Y. Wong, and Paul Mitchell To asses...

85KB Sizes 168 Downloads 84 Views

BRIEF REPORTS Retinal Vascular Caliber, Diabetes, and Retinopathy Annette Kifley, Jie Jin Wang, Sudha Cugati, Tien Y. Wong, and Paul Mitchell To assess the relationship of retinal vessel caliber with diabetes and diabetic retinopathy (DR). DESIGN: Population-based cross-sectional analysis of the Blue Mountains Eye Study, Australia (n ⴝ 3,654, age >49 years). METHODS: Diabetes was defined as physician-diagnosed or fasting blood glucose > 7.0 mmol/l; impaired fasting glucose as fasting glucose 6.1 to 6.9 mmol/l. DR was graded from retinal photographs. Retinal vessel caliber was measured from digitized images. RESULTS: After controlling for age, gender, blood pressure, and other factors, mean retinal venular caliber was significantly wider in participants with moderate-severe nonproliferative DR (severe 262.7 ␮m; moderate 236.7 ␮m) than in nondiabetic participants (221.9 ␮m) or participants with diabetes but no DR (221.2 ␮m) (P < .0001). Mean retinal arteriolar caliber was significantly wider in participants with diabetes (193.5 ␮m) than in nondiabetic participants (190.2 ␮m) (P < .01). CONCLUSIONS: Increasing severity of DR in persons with diabetes is associated with widening of retinal venular caliber. (Am J Ophthalmol 2007;143: 1024 –1026. © 2007 by Elsevier Inc. All rights reserved.) PURPOSE:

A

LTHOUGH IT HAS LONG BEEN SUGGESTED THAT RET-

inal venules are dilated in persons with severe diabetic retinopathy (DR), few studies have demonstrated this in population-based settings using quantitative techniques to assess retinal vessel caliber. Among participants with type 1 diabetes in the Wisconsin Epidemiological Study for Diabetic Retinopathy (WESDR), wider venular caliber was associated with more severe DR.1,2 Another study of young type 1 diabetes subjects, however, showed that wider retinal arteriolar, but not venular, caliber was Accepted for publication Jan 13, 2007. From the Centre for Vision Research, Department of Ophthalmology, University of Sydney, Australia (A.K., J.J.W., S.C., P.M.); Centre for Eye Research Australia, Department of Ophthalmology, University of Melbourne, Australia; and Singapore Eye Research Institute, National University of Singapore, Singapore (T.Y.W.). Inquiries to Paul Mitchell, University of Sydney Department of Ophthalmology (Centre for Vision Research), Eye Clinic, Westmead Hospital, Hawkesbury Rd, Westmead, NSW, Australia, 2145; e-mail: [email protected]

1024

©

2007 BY

associated with early DR.3 Whether similar associations are seen in type 2 diabetes and in the older general population is unclear and is examined here. The Blue Mountains Eye Study is a population-based study of older Australians (age ⱖ49 years) with 3,654 (82.4% of 4,433 eligible) participants at the baseline survey between 1992 and 1994. Ethics approval and the informed consent of participants were obtained. Retinal photographs of six fields were taken through dilated pupils. DR was graded according to the shortened form of the modified Airlie House system. Retinal vessel caliber was measured and summarized from digitized images of right eyes using computer-assisted methods.4 Diabetes was defined as physician-diagnosed diabetes or fasting blood glucose ⱖ126 mg/dl (ⱖ 7.0 mmol/l); impaired fasting glucose as fasting blood glucose 109 to 125 mg/dl (6.1 to 6.9 mmol/l); hypertension as physician-diagnosed hypertension using anti-hypertensive medications, or systolic blood pressure (BP) ⱖ160 mm Hg or diastolic BP ⱖ100 mm Hg. Analysis of covariance and logistic regression were used to compare the retinal vessel calibers of participants without diabetes (controls) and participants with diabetes with and without DR. Of 3,368 participants with retinal vessel caliber data, 255 (7%) had diabetes, including 74 (29%) with DR. We excluded one case of proliferative DR. Table 1 shows that after adjusting for age, gender, smoking, systolic BP, and other risk factors, retinal venular caliber was significantly wider among participants with moderate-severe nonproliferative DR (NPDR) than in participants without diabetes or with diabetes without DR. This association remained significant in models further adjusting for arteriolar caliber (P ⫽ .04). There were no significant differences in venular caliber between participants with mild DR and participants without diabetes. Findings were similar after excluding participants with prior laser therapy (n ⫽ 7, data not shown). Venular caliber was not associated with duration of diabetes or degree of glycemia (data not shown). Table 1 also shows that retinal arteriolar caliber was significantly wider in participants with mild NPDR than in persons without diabetes. This association remained significant with adjustment for venular caliber (P ⫽ .02). Table 2 shows individuals with diabetes, each 20 ␮m (1 standard deviation) increase in retinal venular caliber was associated with a 2.5-fold greater odds of having moderatesevere NPDR. This association was most evident in those with concomitant hypertension, longer diabetes duration, and higher glycemia levels.

ELSEVIER INC. ALL

RIGHTS RESERVED.

0002-9394/07/$32.00

TABLE 1. Retinal Vascular Calibers in Persons With Normal Fasting Glucose, Impaired Fasting Glucose, Diabetes, and Varying Severity of Diabetic Retinopathy Arteriolar Caliber*

By diabetes status Normal fasting glucose Impaired fasting glucose Diabetes By retinopathy status Participants without diabetes Diabetes, no retinopathy Diabetes, early NPDR Minimal NPDR Mild NPDR Diabetes, moderate-severe NPDR Moderate NPDR Severe NPDR

Venular Caliber*

n

Adjusted Mean (SE) ␮m

P value

Adjusted Mean (SE) ␮m

P value

2992 121 255

190.2 (0.4) 191.7 (1.7) 193.5 (1.3)

Ref .4 .01

221.8 (0.4) 223.8 (1.8) 222.6 (1.3)

Ref .3 .5

3113 202 37 16 14 16 12 4

190.2 (0.4) 192.3 (1.4) 197.1 (3.3) 205.4 (5.2) 194.8 (5.4) 201.0 (4.8) 200.9 (5.6) 201.1 (9.4)

Ref .2 .04 .004 .4 .03 .06 .2

221.9 (0.4) 221.2 (1.4) 220.8 (3.3) 225.8 (5.2) 217.7 (5.4) 243.6 (4.8) 236.7 (5.6) 262.7 (9.4)

Ref .6 .7 .4 .4 <.0001 .009 <.0001

NPDR ⫽ nonproliferative diabetic retinopathy; Ref ⫽ reference category; SE ⫽ standard error. *Adjusted for age, gender, smoking (current, past), systolic blood pressure, hemoglobin, fibrinogen, white cell count, body mass index, alcohol intake, and lipid levels (triglyceride, high-density lipoprotein). Boldface indicates significance.

In this population-based study using quantitative methods to measure retinal vessel caliber, we demonstrate significantly wider venular caliber in diabetic persons with

more severe DR than in persons without diabetes or diabetic persons without DR. This finding is consistent with WESDR data, where venular dilatation was associated with

TABLE 2. Cross-Sectional Association Between Retinal Vascular Caliber and Retinopathy Among Participants With Diabetes OR (95% CI) for Retinopathy

n

n (%) Retinopathy

Per SD (20 ␮m) Increase in Arteriolar Caliber*

Per SD (20 ␮m) Increase in Venular Caliber*

Increasing Retinopathy Severity Participants with diabetes No retinopathy Any retinopathy Early NPDR Moderate-severe NPDR By hypertensive status No hypertension Hypertension By glycemia level Lower 50% of group Upper 50% of group By duration of diabetes Less than 10 years 10 years or more

255 202 (79%) 53 (21%) 37 (14%) 16 (6%)

1.0 (ref) 1.2 (0.9–1.8) 1.2 (0.8–1.7) 1.5 (0.8–2.9) Moderate-Severe NPDR vs no

1.0 (ref) 1.1 (0.8–1.6) 0.9 (0.6–1.4) 2.5 (1.2–4.9)† Retinopathy

114 140

7 (6%) 9 (6%)

6.8 (0.8–6.1) 1.4 (0.6–3.0)

1.3 (0.4–4.2) 6.9 (1.6–30.2)‡

124 124

2 (2%) 13 (10%)

— 1.8 (0.6–3.0)

— 2.4 (1.1–5.4)

117 66

3 (3%) 10 (15%)

2.3 (0.5–10.7) 1.4 (0.7–2.8)

1.1 (0.3–4.3) 3.2 (1.2–8.3)

NPDR ⫽ nonproliferative diabetic retinopathy; SD ⫽ standard deviation. *Adjusted for age, gender, diabetes duration, and fasting glucose level. † Significance remained after further adjusting for systolic blood pressure, body mass index, current smoking, and alcohol use (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.5 to 11.4). ‡ Significant interaction between hypertensive status and venular caliber (P ⫽ .04) suggests a true difference between strata.

VOL. 143, NO. 6

BRIEF REPORTS

1025

Alcohol Consumption and the 15-year Cumulative Incidence of Age-related Macular Degeneration

increasing DR severity and four-year DR progression.1,2 These observations suggest that venular dilatation is involved in pathologic processes associated with DR, possibly through mechanisms such as impaired vascular autoregulation and hyperperfusion, tissue hypoxia and ischemia, and aggravating risk factors such as hypertension.5–7 Our finding of a stronger association between wider venular caliber and moderate-severe DR in persons with hypertension appears to support this speculation. We also report an association of wider retinal arteriolar caliber with milder levels of DR, consistent with other smaller studies,3 and with longitudinal findings from the WESDR, in which wider arteriolar caliber predicted DR progression.2 In conclusion, findings from this older Australian population-based sample confirm the association between venular dilatation and DR severity in persons with type 2 diabetes. These data support the concept that retinal vessel caliber, particularly venular caliber, may be a useful surrogate marker of diabetic microvascular complications.

Michael D. Knudtson, Ronald Klein, and Barbara E. K. Klein To investigate alcohol consumption as a risk factor for the 15-year cumulative incidence and progression of age-related macular degeneration (AMD). DESIGN: Prospective population-based study in Beaver Dam, WI with four examinations at five-year intervals initiated in 1988 (n ⴝ 3,509 contributed data for this analysis). METHODS: History of alcohol consumption was obtained via questionnaire. Cumulative incidence of early AMD, exudative AMD, pure geographic atrophy, and progression of AMD were assessed from fundus photographs taken at each examination. RESULTS: Heavy drinking (four or more drinks daily) at baseline was related to the 15-year cumulative incidence of pure geographic atrophy in men (odds ratio, 9.2; 95% confidence interval, 1.7 to 51.2). There were no consistent associations with the amount of beer, wine, or liquor consumption and the incidence or progression of AMD. CONCLUSIONS: Alcohol consumption is unlikely to strongly increase (or decrease) the risk of AMD. (Am J Ophthalmol 2007;143:1026 –1029. © 2007 by Elsevier Inc. All rights reserved.) PURPOSE:

THIS STUDY WAS SUPPORTED BY THE NATIONAL HEALTH and Medical Research Council, Canberra, Australia, Grant no. 302068. The authors indicate no financial conflict of interest. Involved in conception and design (A.K., J.J.W., T.Y.W., P.M.); analysis and interpretation (A.K., J.J.W., S.C., T.Y.W., P.M.); writing the article (A.K., J.J.W., T.Y.W., P.M.); critical revision of the article (A.K., J.J.W., S.C., T.Y.W., P.M.); final approval of the article (A.K., J.J.W., S.C., T.Y.W., P.M.); provision of materials, patients or resources (J.J.W., P.M.); statistical expertise (A.K.); obtaining funding (J.J.W., P.M.); literature search (A.K.); and administrative, technical or logistic support (P.M., J.J.W.).

A

REFERENCES

1. Klein R, Klein BE, Moss SE, et al. Retinal vascular abnormalities in persons with type 1 diabetes: the Wisconsin Epidemiologic Study of Diabetic Retinopathy: XVIII. Ophthalmology 2003;110:2118 –2125. 2. Klein R, Klein BE, Moss SE, et al. The relation of retinal vessel caliber to the incidence and progression of diabetic retinopathy: XIX: the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Arch Ophthalmol 2004; 122:76 – 83. 3. Alibrahim E, Donaghue KC, Rogers S, et al. Retinal vascular caliber and risk of retinopathy in young patients with type 1 diabetes. Ophthalmology 2006;113:1499 –1503. 4. Sherry LM, Wang JJ, Rochtchina E, et al. Reliability of computer-assisted retinal vessel measurement in a population. Clin Experiment Ophthalmol 2002;30:179 –182. 5. Ciulla TA, Harris A, Latkany P, et al. Ocular perfusion abnormalities in diabetes. Acta Ophthalmol Scand 2002;80: 468 – 477. 6. Kohner EM, Patel V, Rassam SM. Role of blood flow and impaired autoregulation in the pathogenesis of diabetic retinopathy. Diabetes 1995;44:603– 607. 7. Lorenzi M, Gerhardinger C. Early cellular and molecular changes induced by diabetes in the retina. Diabetologia 2001;44:791– 804.

1026

AMERICAN JOURNAL

T THE 10-YEAR FOLLOW-UP OF THE BEAVER DAM EYE

Study, history of heavy drinking increased the risk of developing exudative macular degeneration.1 Our previous observation involved a small number of heavy drinkers and incident exudative age-related macular degeneration (AMD) cases. We extend our previous work with five additional years of follow-up. Descriptions of the population, the examinations and AMD grading from retinal photographs have been presented in detail elsewhere.2–5 There were 3,842 persons between ages 43 and 86 years examined at baseline and contributed follow-up information. At each examination, photographs of the retina were taken and AMD was graded.3 Fifteen-year incidence of early AMD (soft indistinct drusen or pigment abnormalities in the presence of drusen), exudative AMD, and pure

Accepted for publication Jan 13, 2007. From the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin. Inquiries to Michael D. Knudtson, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, 610 North Walnut Street, 4th Floor WARF, Madison, WI 53726; e-mail: [email protected] OF

OPHTHALMOLOGY

JUNE 2007