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Choroidal Thickness in Patients with Diabetes and Microalbuminuria
Reports Choroidal Thickness in Patients with Diabetes and Microalbuminuria The association between microalbuminuria and retinopathy in type 2 diabetic patients is controversial. Microalbuminuria has been related to an increased risk of proliferative diabetic retinopathy (DR),1 but its association with the early stages of retinopathy has yet to be fully established. Retinal blood flow is decreased in patients with diabetic kidney disease.2 Because the choroid receives approximately 95% of all ocular blood flow, providing vascular support for the outer layers of the retina, early stage DR may be associated with abnormalities of the choroidal vasculature. Spectral-domain optical coherence tomography (SD-OCT) using the enhanced depth imaging mode has allowed adequate observation and measurement of choroidal thickness (CT) in normal and pathologic eyes.3 Recent reports have shown that CT may be altered in patients with diabetes.4,5 To the best of our knowledge, no analysis of the association between CT and presence of microalbuminuria in patients with diabetes has been reported to date. This study aimed to analyze CT in type 2 diabetic patients with microalbuminuria and with no or mild DR. Consecutive patients with type 2 diabetes and with no or mild DR were recruited from the diabetes outpatient clinic at the Hospital de Clínicas de Porto Alegre, Brazil, between March and September 2013. Participants were divided into 2 groups (normoalbuminuria vs microalbuminuria). Written informed consent was obtained from all patients, and the local ethics committee approved the study protocol. Patients underwent complete ophthalmic examination, stereoscopic color fundus photography, and SD-OCT. Data on known duration of diabetes, glycated hemoglobin, arterial hypertension, and smoking habits were also evaluated. Patients were imaged with a Spectralis high-definition SD-OCT (Heidelberg Engineering Co, Heidelberg, Germany) using the enhanced depth imaging mode. We measured CT in a blinded fashion by an experienced observer from the outer edge of the hyperreflective retinal pigment epithelium to the inner sclera at 500-mm intervals 2500 mm temporal and nasal to the fovea.
Differences in CT between patients with normo- and microalbuminuria were compared using generalized estimating equations to adjust for the inclusion of both eyes of each individual. Generalized estimating equation models were also used to analyze the influence of variables on CT measurements, adjusted for eye, hypertension, smoking habits, and duration of diabetes. A sample size of 64 eyes was calculated to provide 80% power to detect a mean CT difference of 15 mm between the 2 groups, with 95% confidence interval (CI). Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 18.0 (SPSS Inc., Chicago, IL). A prospective, cross-sectional analysis was performed on 62 eyes of 33 patients with diabetes. Baseline characteristics of patients in both groups are described in Table 1 (available at www.aaojournal.org). There were no differences in baseline characteristics between groups (P > 0.05), except for duration of diabetes, which was longer in the microalbuminuric group (11.99.4 vs 9.65.7 years; P ¼ 0.038). Table 2 (available at www.aaojournal.org) shows mean CT at each point of measurement by SD-OCT. The choroid was thinner in the microalbuminuric group (Figure 1). There was a significant difference in mean subfoveal CT between normo- and microalbuminuric groups (284.0312.56 vs 228.8714.44 mm; P ¼ 0.001; 95% CI, 21.88e88.44). Mean CT measurements from 500 mm nasal to 2000 mm temporal to the fovea were also significantly different between groups, but no differences were observed from 500 to 2000 mm nasal to the fovea (Table 2; available at www.aaojournal.org). There were no differences between the left and right eyes of each patient within each group (P ¼ 0.72). Mean CT measurements had no independent association with age, arterial hypertension, duration of diabetes, or smoking habits in the multivariate regression analysis. Previous reports using SD-OCT have demonstrated changes in CT in patients with diabetes. However, this issue remains controversial. In this study, the choroid was thinner in patients with microalbuminuria and CT was significantly different between groups both in the subfoveal region and temporally to the fovea.
Figure 1. Choroidal imaging using spectral-domain optical coherence tomography (SD-OCT) of an eye with diabetes with (A) microalbuminuria and (B) normoalbuminuria. Note the diffuse thinning of the choroid in the upper image and the close proximity of large choroidal vessels to the Bruch’s membraneeretinal pigment epithelium.
1
Ophthalmology Volume -, Number -, Month 2014 This could be attributed to the fact that the greater the thickness of the choroid, the greater the mean difference between CT measurements. Therefore, a larger sample size may be required to confirm these findings nasally to the fovea. Microalbuminuria represents a state of generalized vascular dysfunction that leads to functional and structural abnormalities in blood vessels, including endothelial dysfunction, reduced vascular compliance, and atherosclerosis. This could explain the reduction in CT observed in these patients and may be interpreted as early evidence of microvascular choroidal damage in patients with diabetes, even before the first microaneurysms can be detected. A limitation of this study is the relatively small sample size and failure to control for potential confounders, such as known diurnal variations in CT. In addition, although CT was measured manually by an experienced retina specialist (D.L.) blinded to the identity and clinical data of patients, we did not establish a grading system to allow reproducibility of CT measurements. Nevertheless, strict inclusion criteria were established for both groups, ensuring 2 wellmatched groups with respect to meaningful characteristics. In conclusion, our findings showed a significantly thinner choroid in patients with diabetes and microalbuminuria, especially in the subfoveal region and temporally to the fovea. These data suggest that decreased CT in patients with diabetes and microalbuminuria may be a sign of microvascular choroidal damage to the eye, even before clinical damage to retinal vessels becomes evident by microaneurysms and hemorrhage, and this could be used as a marker for the risk of developing early-stage DR. However, larger longitudinal studies are needed to confirm these findings and elucidate the role of CT in the diagnosis and prognosis of DR and systemic microvascular disease in patients with type 2 diabetes.
2
LUCAS B. FARIAS, MD1 DANIEL LAVINSKY, MD, PHD1 WAGNER M. SCHNEIDER, MD1 LUCIANO GUIMARÃES, MSC2 JACÓ LAVINSKY, MD, PHD1 LUIS H. CANANI, MD, PHD3 1 Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; 2Epidemiology and Biostatistics Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; 3 Departament of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
References 1. Cruickshanks KJ, Ritter LL, Klein R, Moss SE. The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 1993;100:862–7. 2. Nagaoka T, Yoshida A. Relationship between retinal blood flow and renal function in patients with type 2 diabetes and chronic kidney disease. Diabetes Care 2013;36:957–61. 3. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. 4. Regatieri CV, Branchini L, Carmody J, et al. Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina 2012;32:563–8. 5. Xu J, Xu L, Du KF, et al. Subfoveal choroidal thickness in diabetes and diabetic retinopathy. Ophthalmology 2013;120: 2023–8.
Differences in CT between patients with normo- and microalbuminuria were compared using generalized estimating equations to adjust for the inclusion of both eyes of each individual. Generalized estimating equation models were also used to analyze the influence of variables on CT measurements, adjusted for eye, hypertension, smoking habits, and duration of diabetes. A sample size of 64 eyes was calculated to provide 80% power to detect a mean CT difference of 15 mm between the 2 groups, with 95% confidence interval (CI). Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 18.0 (SPSS Inc., Chicago, IL). A prospective, cross-sectional analysis was performed on 62 eyes of 33 patients with diabetes. Baseline characteristics of patients in both groups are described in Table 1 (available at www.aaojournal.org). There were no differences in baseline characteristics between groups (P > 0.05), except for duration of diabetes, which was longer in the microalbuminuric group (11.99.4 vs 9.65.7 years; P ¼ 0.038). Table 2 (available at www.aaojournal.org) shows mean CT at each point of measurement by SD-OCT. The choroid was thinner in the microalbuminuric group (Figure 1). There was a significant difference in mean subfoveal CT between normo- and microalbuminuric groups (284.0312.56 vs 228.8714.44 mm; P ¼ 0.001; 95% CI, 21.88e88.44). Mean CT measurements from 500 mm nasal to 2000 mm temporal to the fovea were also significantly different between groups, but no differences were observed from 500 to 2000 mm nasal to the fovea (Table 2; available at www.aaojournal.org). There were no differences between the left and right eyes of each patient within each group (P ¼ 0.72). Mean CT measurements had no independent association with age, arterial hypertension, duration of diabetes, or smoking habits in the multivariate regression analysis. Previous reports using SD-OCT have demonstrated changes in CT in patients with diabetes. However, this issue remains controversial. In this study, the choroid was thinner in patients with microalbuminuria and CT was significantly different between groups both in the subfoveal region and temporally to the fovea.
Figure 1. Choroidal imaging using spectral-domain optical coherence tomography (SD-OCT) of an eye with diabetes with (A) microalbuminuria and (B) normoalbuminuria. Note the diffuse thinning of the choroid in the upper image and the close proximity of large choroidal vessels to the Bruch’s membraneeretinal pigment epithelium.
1
Ophthalmology Volume -, Number -, Month 2014 This could be attributed to the fact that the greater the thickness of the choroid, the greater the mean difference between CT measurements. Therefore, a larger sample size may be required to confirm these findings nasally to the fovea. Microalbuminuria represents a state of generalized vascular dysfunction that leads to functional and structural abnormalities in blood vessels, including endothelial dysfunction, reduced vascular compliance, and atherosclerosis. This could explain the reduction in CT observed in these patients and may be interpreted as early evidence of microvascular choroidal damage in patients with diabetes, even before the first microaneurysms can be detected. A limitation of this study is the relatively small sample size and failure to control for potential confounders, such as known diurnal variations in CT. In addition, although CT was measured manually by an experienced retina specialist (D.L.) blinded to the identity and clinical data of patients, we did not establish a grading system to allow reproducibility of CT measurements. Nevertheless, strict inclusion criteria were established for both groups, ensuring 2 wellmatched groups with respect to meaningful characteristics. In conclusion, our findings showed a significantly thinner choroid in patients with diabetes and microalbuminuria, especially in the subfoveal region and temporally to the fovea. These data suggest that decreased CT in patients with diabetes and microalbuminuria may be a sign of microvascular choroidal damage to the eye, even before clinical damage to retinal vessels becomes evident by microaneurysms and hemorrhage, and this could be used as a marker for the risk of developing early-stage DR. However, larger longitudinal studies are needed to confirm these findings and elucidate the role of CT in the diagnosis and prognosis of DR and systemic microvascular disease in patients with type 2 diabetes.
2
LUCAS B. FARIAS, MD1 DANIEL LAVINSKY, MD, PHD1 WAGNER M. SCHNEIDER, MD1 LUCIANO GUIMARÃES, MSC2 JACÓ LAVINSKY, MD, PHD1 LUIS H. CANANI, MD, PHD3 1 Department of Ophthalmology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; 2Epidemiology and Biostatistics Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; 3 Departament of Endocrinology, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil
References 1. Cruickshanks KJ, Ritter LL, Klein R, Moss SE. The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 1993;100:862–7. 2. Nagaoka T, Yoshida A. Relationship between retinal blood flow and renal function in patients with type 2 diabetes and chronic kidney disease. Diabetes Care 2013;36:957–61. 3. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. 4. Regatieri CV, Branchini L, Carmody J, et al. Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina 2012;32:563–8. 5. Xu J, Xu L, Du KF, et al. Subfoveal choroidal thickness in diabetes and diabetic retinopathy. Ophthalmology 2013;120: 2023–8.