Current Eye Research
ISSN: 0271-3683 (Print) 1460-2202 (Online) Journal homepage: http://www.tandfonline.com/loi/icey20
Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani & Akitoshi Yoshida To cite this article: Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani & Akitoshi Yoshida (2015) Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects, Current Eye Research, 40:10, 1040-1045 To link to this article: http://dx.doi.org/10.3109/02713683.2014.971930
Published online: 20 Oct 2014.
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Current Eye Research, 2015; 40(10): 1040–1045 Copyright ! Taylor & Francis Group, LLC ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2014.971930
ORIGINAL ARTICLE
Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani and Akitoshi Yoshida
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Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan
ABSTRACT Purpose: The purpose of this study was to investigate the effects of aging on anteroposterior tortuosity of the retinal vein at the arteriovenous (AV) crossing in healthy subjects. Methods: We examined 48 eyes of 24 healthy older Japanese subjects (460 years), and, as controls, 42 eyes of 21 healthy younger Japanese subjects (530 years). Retinal vein images at the AV crossing were obtained by optical coherence tomography. The depth of the vein was measured vertically from the outer border of the retinal pigment epithelium to the outer vein wall. We defined ‘‘m’’ as the deepest point of the vein at the AV crossing and ‘‘M’’ as the shallowest point. To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio m/M. Results: Mean m, M, and m/M in older subjects were 76.5 ± 13.1 mm, 142.7 ± 21.2 mm, and 0.52 ± 0.09, respectively. In younger control subjects, the values were 64.1 ± 12.6 mm, 139.9 ± 22.4 mm, and 0.46 ± 0.06. The values of ‘‘M’’ were not significantly different between groups, whereas both ‘‘m/M’’ and ‘‘m’’ were significantly (p = 0.021) lower in the older subjects than in the younger subjects. Conclusion: Anteroposterior tortuosity of the retinal vein was evaluated based on the maximum and minimum retinal vein depth measurements at the AV crossing using optical coherence tomography. Anteroposterior tortuosity of the retinal vein at the AV crossing is increased with age. Keywords: AV crossing, OCT, tortuosity
INTRODUCTION
dimensionally have been proposed to determine the tortuosity in three dimensionally.3,7 However, the anteroposterior run of the vein at the AV crossing is difficult to evaluate because of the location of the artery above the vein. Several histologic studies in healthy humans have demonstrated that the direction of the retinal vein changes abruptly as it passes beneath the artery at the AV crossing.8,9 Vertical tortuosity of the retinal vein at the AV crossing, however, has not been precisely evaluated under physiologic conditions. Recent developments of Spectralis HRA + optical coherence tomography (OCT)10–13 allow for noninvasive evaluation of the choroidal structure as well as the retina by providing much clearer retinal images
The retina comprises unique tissue that allows for direct observation of relatively large vessels, including the arteriovenous (AV) crossing. Retinal AV crossings are susceptible to branch retinal vein occlusion (BRVO) and are thus very important points clinically.1,2 There are many studies formulated the vessel tortuosity 2 dimensionally.3–6 For example, Azegrouz et al.4 reported the mathematic method to estimate horizontal tortuosity simply as the ratio of the length of the curve (L) to the distance between the ends of it (C): tortuosity = L/C. In addition, several ways to adapt methods estimating tortuosity in two
Received 23 April 2014; revised 11 September 2014; accepted 28 September 2014; published online 20 October 2014 Correspondence: Kenji Sogawa, MD, PhD, Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, Japan. Tel: +81 166 68 2543. Fax: +81 166 68 2549. E-mail: [email protected]
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Tortuosity of the Retinal Vein at AV Crossings
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than conventional time-domain (TD) OCT. Despite the high resolution of the images, however, few studies have focused on the retinal vessels using Spectralis HRA + OCT. In a recent clinical study, Muraoka et al. evaluated retinal vessel diameter in normal and hypertensive subjects using the Spectralis HRA + OCT.14 They demonstrated that the retinal vein runs deep under the artery and the venous lumen appears to be preserved at the AV crossing in BRVO eyes.15 Therefore, we hypothesized that retinal vein tortuosity at the AV crossing is related to aging. In the present study, we used the Spectralis HRA + OCT to evaluate for the first time the extent of the anteroposterior tortuosity of the retinal vein at the AV crossing under physiologic conditions in healthy volunteers.
METHODS The study adheres to the Declaration of Helsinki. The institutional review board at Asahikawa Medical University approved the current study. All subjects provided informed consent before the examinations. Forty-eight eyes of 24 healthy older Japanese subjects (460 years) were enrolled in the study and 42 eyes of 21 healthy younger Japanese subjects (530 years) were used as controls. Patients were excluded if they were current smokers or had diabetes, heart disease, impaired renal function, hypercholesterolemia, systemic hypertension (4140/90 mmHg), ocular disease, excessive myopia (5 6.0 D), or a history of ophthalmic surgery. In addition, eyes were also excluded if they had no first-order or second-order AV crossings and the retinal vein lay anterior to the artery at the AV crossing point. The refractive error and intraocular pressure were measured using a Tonoref RKT-7000 autorefractometer (Nidek Inc., Gamagori, Japan). Axial length was measured using the IOL Master 500 (Carl Zeiss Meditec Inc., Jena, Germany). Systolic and diastolic blood pressures were measured using a sphygmomanometer (Omron Inc., Aichi, Japan) with subjects in the sitting position. The characteristics of the study subjects are shown in Table 1. The retinal vein images at the AV crossing were obtained using the Spectralis HRA + OCT (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). We measured first-order or second-order AV crossings at least 1 disc diameter from the optic disc. The retinal vein was scanned sequentially from two directions (25 sections of 5 each): one direction was a longitudinal image along the vein and the other direction was a cross-sectional image (Figures 1 and 2). Each section was averaged with 100 scans obtained at the same position. At the AV crossing point, the depth of the vein was measured vertically from the outer border of the retinal pigment epithelium (RPE) to the outer vein wall (Figure 2b). The horizontal retinal vein depth was Copyright ! 2015 Taylor & Francis Group, LLC
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TABLE 1 Clinical and biochemical characteristics of the study subjects. Parameter No. men/women Age (years) SBP (mmHg) DBP (mmHg) HR (bpm) IOP (mmHg) Refractive error (D) Axial length (mm) No. AV crossing m (mm) M (mm) m/M Da (mm) Dv (mm)
Younger
Older
42 (24/18) 26.2 ± 2.9 122.5 ± 13.1 75.4 ± 10.6 70.8 ± 8.4 12.9 ± 2.3 0.9 ± 1.2 25.9 ± 2.4 52 76.5 ± 13.1 142.7 ± 21.2 0.52 ± 0.09 89.2 ± 8.8 112.9 ± 12.8
45 (24/21) 65.8 ± 4.8 128.2 ± 11.6 76.3 ± 13.1 68.2 ± 9.1 13.2 ± 2.2 0.6 ± 1.3 25.4 ± 2.1 59 64.1 ± 12.6 * 139.9 ± 22.4 0.46 ± 0.10** 88.6 ± 9.3 115.1 ± 13.2
SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; IOP, intraocular pressure; D, diopters; AV, arteriovenous; m, the deepest point of vein at AV crossing; M, the shallowest point of vein where it was 300 mm upper stream from the AV crossing; Da, inner arterial diameter; Dv, inner venous diameter; mm, millimeter; mm, micrometer. Data are means ± standard error of the mean. *p = 0.018 and **p = 0.021 versus younger values.
measured retrospectively using the planimetric scale software in the device. The retinal vein depth was averaged based on longitudinal and cross-sectional images (Figure 2b, d, and f). We defined ‘‘m’’ as the deepest point of the vein at the AV crossing point where the mean distance from the RPE to the outer vein wall was the shortest, and mean ‘‘M’’ as the shallowest point of the vein 300 mm upstream from the ‘‘m’’ point (Figure 2b, d, and f). To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio ‘‘m/M’’. We also measured the inner vessel diameter of the retinal vein and artery using the Spectralis OCT method (Figure 2).14 The inner diameters of the retinal artery and retinal vein were measured at the AV crossing and 300 mm upstream from the AV crossing, respectively. The retinal artery and vein inner diameters were also averaged based on longitudinal and cross-sectional images (Figure 2). Independent observers measured m, M, and the inner vessel diameter. A blinded observer (TT) analyzed the data to determine the correlation between the tortuosity and the other parameters.
Statistical Analysis All data are expressed as the mean ± the standard error of the mean. The significance of differences in data between younger subjects and older subjects was determined with the Mann–Whitney U test. Commercially available software (SPSS v. 17.0J for Windows; SPSS Inc., Chicago, IL) was used for all
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FIGURE 1 Typical sectional OCT images of younger and older eyes. (a) OCT image of an eye from the group of younger subjects was obtained along the arrow A. (b) Longitudinal image of the vein along the arrow A. At the AV crossing point, the retinal vein ran beneath the retinal artery above the inner and outer segments of the retinal photoreceptors (IS/OS line) level. There was no venous narrowing at the AV crossing. (c) Sectional images of older eyes were also obtained along arrows A. (d) Longitudinal image of the vein at the AV crossing along arrow A. The retinal vein ran beneath the retinal artery to the IS/OS line level. There was no venous narrowing at the AV crossing.
statistical analyses. A p value of less than 0.05 was considered statistically significant.
RESULTS The patient characteristics are shown in Table 1. Mean age of the younger control subjects was 26.2 ± 2.9 years (range 21–30 years); the mean refractive error was 0.9 ± 1.2 D (range 2.00 to 0.25 D) and the mean axial length was 25.9 ± 2.4 mm. The mean age of the older subjects was 65.8 ± 4.8 years (range 61–73 years); the mean refractive error was 0.6 ± 1.3 D (range 2.50 to 1.25 D), and the mean axial length was 25.4 ± 2.1 mm. Among the 42 younger eyes, there were 82 firstorder and second-order AV crossings in the vascular arcade. A retinal artery was located anterior to the vein in 52 (n = 52) of the 82 AV crossings. Among the 48 older subject eyes, there were 93 AV crossings in the vascular arcade, and 59 artery-over-vein crossings. Representative images of younger and older eyes are shown in Figure 1(b) and (d) In 27 eyes (64.3 %) in younger subjects, the retinal vein was located above the inner and outer segments of the retinal photoreceptors (IS/OS line) level at the AV crossing
(Figure 1b). In contrast, in 30 eyes (66.7 %) in older subjects, the retinal vein ran beneath the retinal artery at the AV crossing (Figure 1d). There was no venous narrowing at the AV crossing in younger or older eyes (Figure 1b and d). In older subjects, mean m, M, m/M, artery inner diameter, and vein inner diameter were 76.5 ± 13.1 mm, 142.7 ± 21.2 mm, 0.52 ± 0.09, 89.2 ± 8.8 mm, and 112.9 ± 12.8 mm, respectively. In contrast, in younger subjects, mean m, M, m/M, artery inner diameter, and vein inner diameter were 64.1 ± 12.6 mm, 139.9 ± 22.4 mm, 0.46 ± 0.06, 88.6 ± 9.3 mm, and 115.1 ± 13.2 mm, respectively. The values of M and artery and vein inner diameters did not differ significantly between younger and older subjects. Both ‘‘m/M’’ and ‘‘m’’ were significantly (p = 0.021 and p = 0.018) lower in older subjects than in younger subjects (Figure 3).
DISCUSSION In the present study, the retinal vein at the AV crossing evaluated by vein depth measurement using HRA + OCT images was more curved anteroposteriorly in older eyes compared with younger eyes. Many studies have evaluated AV crossings Current Eye Research
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Tortuosity of the Retinal Vein at AV Crossings
FIGURE 2 OCT images of older eyes to evaluate the tortuosity of vein. (a) Sectional images of an eye from the group of older subjects were obtained along arrows, A, B, and C. (b) This image is the same as that in Figure 1(d). Hyper-reflective signs were observed at the top and bottom of the artery (black arrowhead). We measured ‘‘M’’, ‘‘m’’, vein diameter (Dv), and artery diameter (Da). (c) Crosssectional image of the retinal vein along arrow B, 300 mm away from the AV crossing. Hyper-reflective signs were observed at the top and bottom of the vein (black arrowhead). (d) This image is the same as that in Figure 2(c). We measured ‘‘M’’ and Dv at this point. (e) Cross-sectional images of the vein along arrow C at the AV crossing point. Hyper-reflective signs of the retinal vein were weak at the AV crossing. The IS/OS line was also weak because of the location of the above artery. (f) This image is the same as that in Figure 2(e). We measured ‘‘m’’ and Da here. Copyright ! 2015 Taylor & Francis Group, LLC
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FIGURE 3 Mean ‘‘m/M’’ of younger and older subjects. ‘‘m/M’’ was significantly decreased in older eyes compared with younger eyes. The bottom and the top of the box are the first and third quartiles, and the band inside the box is the median. The ends of the whiskers represent several possible alternative values. *p = 0.021 versus younger values.
histologically.8,9 Despite the importance of observing the morphologic features of vessels under physiologic conditions, such as blood flow, few studies have performed such precise evaluations. Some color fundus photograph studies have focused on AV crossings16 but AV crossings can only be observed horizontally on fundus photographs, and the retinal vein cannot be observed anteroposteriorly under the artery at the AV crossings. Conventional TD-OCT has a low resolution and it is thus difficult to assess the retinal structure precisely. The recently developed HRA + OCT is useful for noninvasive investigation of changes of the retinal structure because it has a higher resolution and faster scanning speed and image processing than the TDOCT.17,18 Muraoka et al.14,15,19 evaluated the anteroposterior tortuosity of the retinal vein in eyes with BRVO or central retinal vein occlusion with HRA + OCT images. They observed the anteroposterior tortuosity of the retinal vein at the AV crossing in healthy human eyes.19 There are no reports, however, of the extent of retinal vein tortuosity anteroposteriorly at the AV crossing in healthy eyes, especially in older subjects. Our findings support existing data indicating that the retinal vein runs deep under the artery and that the venous lumen is preserved at the AV crossing in normal eyes. In the present study, we were able to evaluate the anteroposterior tortuosity of the retinal vein at the AV crossing based on the ratio m/M determined from HRA + OCT images. There is no index for evaluating the anteroposterior tortuosity of the retinal vein. In the present study, we used m and M to calculate the ratio m/M as the extent of retinal vein tortuosity. In some older subjects, visualization of the junction between the IS/OS line was blocked by the retinal vein at the AV crossing (Figure 1d). In contrast, in all eyes of both older and
younger subjects, the RPE line was clearly observed at the AV crossing (Figure 1b and d). In addition, it was easy to detect the choroidal side outer hyper-reflective line of the retinal vein (Figure 1b and d). Therefore, m and M accurately represent the depth of the retinal vein. In this study, we used m/M as the index of the extent of retinal vein tortuosity. If all the retinal veins ran at a right angle to the artery at the AV crossing, the radius of the vein curvature might be the index of vein tortuosity. Retinal veins, however, cross the artery at various angles. When the angle of the AV crossing is small, the length of the vein under the artery is longer when it crosses at a right angle, and thus the radius of the vein curvature will be large. The index of the venous radius curvature was influenced by the angle of the AV crossing. Taken together, it is reasonable to assume that m/M represents the tortuosity of the retinal vein at the AV crossing. In the present study, we revealed for the first time that m/M was significantly smaller in older eyes than in younger eyes (Figure 3), suggesting that retinal veins are more curved at the AV crossing in older eyes than in younger eyes. This finding resulted from the significantly lower m in the older subjects (Table 1). The retinal vein ran deeper at the AV crossing point in older eyes than in younger eyes. We speculate that this might be due to increased arterial and venous wall thickness in older subjects, because there was no significant difference between the inner diameter of the artery or vein at the AV crossing in the two groups (Table 1). Michelson et al.20 reported that both arterial and venous vessel wall thicknesses, calculated as the difference in vessel diameter and flow diameter by scanning laser Doppler flowmetry, are increased by aging. Using the same method as in the present study, Muraoka et al.14 reported that both arterial and venous wall thicknesses positively correlated with age in eyes without hypertension. Based on these findings, we speculate that more thickened arterial and venous walls at the AV crossing in older eyes might lead to deeper veins in the retina at the AV crossing. The present study has some limitations. First, although HRA-OCT provides markedly clearer images than conventional OCT, we could not precisely measure the vein wall thickness at the AV crossing point, because it was difficult to determine the inner vein wall due to weakening of signal vein images by the above artery, especially in older eyes (Figure 2f). For the same reason, we were also unable to measure the inner diameter of the vein precisely at the AV crossing. Second, the result of the present study was influenced by arteriosclerosis to some extent, especially in the older subjects, because it is well known that arteriosclerosis is increased in older subjects. Some groups reported that arterial stiffness, evaluated by measuring the cardio-ankle vascular index, is increased by aging.21,22 Arteriosclerosis, however, cannot be excluded from the older group Current Eye Research
Tortuosity of the Retinal Vein at AV Crossings and thus it is inevitable that our result was affected by arteriosclerosis. Additional clinical studies are needed to evaluate the influences of arteriosclerosis on venous anteroposterior tortuosity. In conclusion, we measured the retinal vein depth and the arterial and venous inner diameter at the AV crossing using HRA-OCT and evaluated the anteroposterior tortuosity of the retinal vein by measuring the maximum and minimum retinal vein depths at the AV crossing. We found that venous anteroposterior tortuosity at the AV crossing increases with increased age.
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DECLARATION OF INTEREST The authors report that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES 1. Weinberg D, Dodwell DG, Fern SA. Anatomy of arteriovenous crossings in branch retinal vein occlusion. Am J Ophthalmol 1990;109:298–302. 2. Staurenghi G, Lonati C, Aschero M, Orzalesi N. Arteriovenous crossing as a risk factor in branch retinal vein occlusion. Am J Ophthalmol 1994;117:211–213. 3. T¸a˘lu S. Characterization of retinal vessel networks in human retinal imagery using quantitative descriptors. HVM Bioflux 2012;5:52–57. 4. Azegrouz H, Trucco E, Dhillon B, MacGillivrya T, MacCormick IJ. Thickness dependent tortuosity estimation for retinal blood vessels. Conf Proc IEEE Eng Med Biol Soc 2006;1:4675–4678. 5. Capowski JJ, Kylstra JA, Freedman SF. A numeric index based on spatial frequency for the tortuosity of retinal vessels and its application to plus disease in retinopathy of prematurity. Retina 1995;15:490–500. 6. Grisan E, Foracchia M, Ruggeri A. A novel method for the automatic grading of retinal vessel tortuosity. IEEE Trans Med Imaging 2008;27:310–319. 7. Jhonson MJ, Dougherty G. Robust measures of threedimensional vascular tortuosity based on the minimum curvature of approximating polynomial spline fits to the vessel mid-line. Med Eng Phys 2007;29:677–690. 8. Seitz R. The retinal blood vessels. Comparative ophthalmoscopic and histological studies on the healthy and pathologically changed eye. Buch Augenarzt 1962;40: 1–175. 9. Jefferies P, Clemett R, Day T. An anatomical study of retinal arteriovenous crossings and their role in the pathogenesis
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of retinal branch vein occlusions. Aust N Z Ophthalmol 1993;21:213–217. Spaide RF. Enhanced depth imaging optical coherence tomography of retinal pigment epithelial detachment in age-related macular degeneration. Am J Ophthalmol 2009; 147:644–652. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008;146:496–500. Maruko I, Iida T, Sugano Y, Ojima A, Sekiryu T. Subfoveal choroidal thickness in fellow eyes of patients with central serous chorioretinopathy. Retina 2011;31:1603–1608. Park HY, Park CK. Diagnostic capability of lamina cribrosa thickness by enhanced depth imaging and factors affecting thickness in patients with glaucoma. Ophthalmology 2013; 120:745–752. Muraoka Y, Tsujikawa A, Kumagai K, Akiba M, Ogino K, Murakami T, et al. Age- and hypertension-dependent changes in retinal vessel diameter and wall thickness: an optical coherence tomography study. Am J Ophthalmol 2013;156:706–714. Muraoka Y, Tsujikawa A, Murakami T, Ogino K, Kumagai K, Miyamoto K, et al. Morphologic and functional changes in retinal vessels associated with branch retinal vein occlusion. Ophthalmology 2013;120:91–99. Waisbren EC, Salz DA, Brown MM, Brown GC. Vascular crossing patterns in patients with systemic arterial hypertension. Br J Ophthalmol 2013;97:781–784. Takahashi A, Yoshida A, Nagaoka T, Takamiya A, Sato E, Kagokawa H, et al. Idiopathic full-thickness macular holes and the vitreomacular interface: a high-resolution spectraldomain optical coherence tomography study. Am J Ophthalmol 2012;154:881–892 e882. Liu M, Wolfson Y, Bressler SB, Do D, Ying HS, Bressler NM. Comparison of time- and spectral-domain optical coherence tomography in management of diabetic macular edema. Invest Ophthalmol Vis Sci 2014;55: 1307–1377. Muraoka Y, Tsujikawa A, Kumagai K, Akagi-Kurashige Y, Ogino K, Murakami T, et al. Retinal vessel tortuosity associated with central retinal vein occlusion: an optical coherence tomography study. Invest Ophthalmol Vis Sci 2014;55:134–141. Michelson G, Warntges S, Baleanu D, Welzenbach J, OhnoJinno A, Pogorelov P, et al. Morphometric age-related evaluation of small retinal vessels by scanning laser Doppler flowmetry: determination of a vessel wall index. Retina 2007;27:490–498. Shirai K, Utino J, Otsuka K, Takata M. A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb 2006;13:101–107. Kadota K, Takamura N, Aoyagi K, Yamasaki H, Usa T, Nakazato M, et al. Availability of cardio-ankle vascular index (CAVI) as a screening tool for atherosclerosis. Circ J 2008;72:304–308.
ISSN: 0271-3683 (Print) 1460-2202 (Online) Journal homepage: http://www.tandfonline.com/loi/icey20
Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani & Akitoshi Yoshida To cite this article: Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani & Akitoshi Yoshida (2015) Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects, Current Eye Research, 40:10, 1040-1045 To link to this article: http://dx.doi.org/10.3109/02713683.2014.971930
Published online: 20 Oct 2014.
Submit your article to this journal
Article views: 35
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icey20 Download by: [University of Cambridge]
Date: 06 November 2015, At: 04:40
Current Eye Research, 2015; 40(10): 1040–1045 Copyright ! Taylor & Francis Group, LLC ISSN: 0271-3683 print / 1460-2202 online DOI: 10.3109/02713683.2014.971930
ORIGINAL ARTICLE
Anteroposterior Tortuosity of the Retinal Vein at Arteriovenous Crossings in Healthy Subjects Kenji Sogawa, Taiji Nagaoka, Tomofumi Tani and Akitoshi Yoshida
Downloaded by [University of Cambridge] at 04:40 06 November 2015
Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan
ABSTRACT Purpose: The purpose of this study was to investigate the effects of aging on anteroposterior tortuosity of the retinal vein at the arteriovenous (AV) crossing in healthy subjects. Methods: We examined 48 eyes of 24 healthy older Japanese subjects (460 years), and, as controls, 42 eyes of 21 healthy younger Japanese subjects (530 years). Retinal vein images at the AV crossing were obtained by optical coherence tomography. The depth of the vein was measured vertically from the outer border of the retinal pigment epithelium to the outer vein wall. We defined ‘‘m’’ as the deepest point of the vein at the AV crossing and ‘‘M’’ as the shallowest point. To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio m/M. Results: Mean m, M, and m/M in older subjects were 76.5 ± 13.1 mm, 142.7 ± 21.2 mm, and 0.52 ± 0.09, respectively. In younger control subjects, the values were 64.1 ± 12.6 mm, 139.9 ± 22.4 mm, and 0.46 ± 0.06. The values of ‘‘M’’ were not significantly different between groups, whereas both ‘‘m/M’’ and ‘‘m’’ were significantly (p = 0.021) lower in the older subjects than in the younger subjects. Conclusion: Anteroposterior tortuosity of the retinal vein was evaluated based on the maximum and minimum retinal vein depth measurements at the AV crossing using optical coherence tomography. Anteroposterior tortuosity of the retinal vein at the AV crossing is increased with age. Keywords: AV crossing, OCT, tortuosity
INTRODUCTION
dimensionally have been proposed to determine the tortuosity in three dimensionally.3,7 However, the anteroposterior run of the vein at the AV crossing is difficult to evaluate because of the location of the artery above the vein. Several histologic studies in healthy humans have demonstrated that the direction of the retinal vein changes abruptly as it passes beneath the artery at the AV crossing.8,9 Vertical tortuosity of the retinal vein at the AV crossing, however, has not been precisely evaluated under physiologic conditions. Recent developments of Spectralis HRA + optical coherence tomography (OCT)10–13 allow for noninvasive evaluation of the choroidal structure as well as the retina by providing much clearer retinal images
The retina comprises unique tissue that allows for direct observation of relatively large vessels, including the arteriovenous (AV) crossing. Retinal AV crossings are susceptible to branch retinal vein occlusion (BRVO) and are thus very important points clinically.1,2 There are many studies formulated the vessel tortuosity 2 dimensionally.3–6 For example, Azegrouz et al.4 reported the mathematic method to estimate horizontal tortuosity simply as the ratio of the length of the curve (L) to the distance between the ends of it (C): tortuosity = L/C. In addition, several ways to adapt methods estimating tortuosity in two
Received 23 April 2014; revised 11 September 2014; accepted 28 September 2014; published online 20 October 2014 Correspondence: Kenji Sogawa, MD, PhD, Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido 078-8510, Japan. Tel: +81 166 68 2543. Fax: +81 166 68 2549. E-mail: [email protected]
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than conventional time-domain (TD) OCT. Despite the high resolution of the images, however, few studies have focused on the retinal vessels using Spectralis HRA + OCT. In a recent clinical study, Muraoka et al. evaluated retinal vessel diameter in normal and hypertensive subjects using the Spectralis HRA + OCT.14 They demonstrated that the retinal vein runs deep under the artery and the venous lumen appears to be preserved at the AV crossing in BRVO eyes.15 Therefore, we hypothesized that retinal vein tortuosity at the AV crossing is related to aging. In the present study, we used the Spectralis HRA + OCT to evaluate for the first time the extent of the anteroposterior tortuosity of the retinal vein at the AV crossing under physiologic conditions in healthy volunteers.
METHODS The study adheres to the Declaration of Helsinki. The institutional review board at Asahikawa Medical University approved the current study. All subjects provided informed consent before the examinations. Forty-eight eyes of 24 healthy older Japanese subjects (460 years) were enrolled in the study and 42 eyes of 21 healthy younger Japanese subjects (530 years) were used as controls. Patients were excluded if they were current smokers or had diabetes, heart disease, impaired renal function, hypercholesterolemia, systemic hypertension (4140/90 mmHg), ocular disease, excessive myopia (5 6.0 D), or a history of ophthalmic surgery. In addition, eyes were also excluded if they had no first-order or second-order AV crossings and the retinal vein lay anterior to the artery at the AV crossing point. The refractive error and intraocular pressure were measured using a Tonoref RKT-7000 autorefractometer (Nidek Inc., Gamagori, Japan). Axial length was measured using the IOL Master 500 (Carl Zeiss Meditec Inc., Jena, Germany). Systolic and diastolic blood pressures were measured using a sphygmomanometer (Omron Inc., Aichi, Japan) with subjects in the sitting position. The characteristics of the study subjects are shown in Table 1. The retinal vein images at the AV crossing were obtained using the Spectralis HRA + OCT (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany). We measured first-order or second-order AV crossings at least 1 disc diameter from the optic disc. The retinal vein was scanned sequentially from two directions (25 sections of 5 each): one direction was a longitudinal image along the vein and the other direction was a cross-sectional image (Figures 1 and 2). Each section was averaged with 100 scans obtained at the same position. At the AV crossing point, the depth of the vein was measured vertically from the outer border of the retinal pigment epithelium (RPE) to the outer vein wall (Figure 2b). The horizontal retinal vein depth was Copyright ! 2015 Taylor & Francis Group, LLC
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TABLE 1 Clinical and biochemical characteristics of the study subjects. Parameter No. men/women Age (years) SBP (mmHg) DBP (mmHg) HR (bpm) IOP (mmHg) Refractive error (D) Axial length (mm) No. AV crossing m (mm) M (mm) m/M Da (mm) Dv (mm)
Younger
Older
42 (24/18) 26.2 ± 2.9 122.5 ± 13.1 75.4 ± 10.6 70.8 ± 8.4 12.9 ± 2.3 0.9 ± 1.2 25.9 ± 2.4 52 76.5 ± 13.1 142.7 ± 21.2 0.52 ± 0.09 89.2 ± 8.8 112.9 ± 12.8
45 (24/21) 65.8 ± 4.8 128.2 ± 11.6 76.3 ± 13.1 68.2 ± 9.1 13.2 ± 2.2 0.6 ± 1.3 25.4 ± 2.1 59 64.1 ± 12.6 * 139.9 ± 22.4 0.46 ± 0.10** 88.6 ± 9.3 115.1 ± 13.2
SBP, systolic blood pressure; DBP, diastolic blood pressure; HR, heart rate; IOP, intraocular pressure; D, diopters; AV, arteriovenous; m, the deepest point of vein at AV crossing; M, the shallowest point of vein where it was 300 mm upper stream from the AV crossing; Da, inner arterial diameter; Dv, inner venous diameter; mm, millimeter; mm, micrometer. Data are means ± standard error of the mean. *p = 0.018 and **p = 0.021 versus younger values.
measured retrospectively using the planimetric scale software in the device. The retinal vein depth was averaged based on longitudinal and cross-sectional images (Figure 2b, d, and f). We defined ‘‘m’’ as the deepest point of the vein at the AV crossing point where the mean distance from the RPE to the outer vein wall was the shortest, and mean ‘‘M’’ as the shallowest point of the vein 300 mm upstream from the ‘‘m’’ point (Figure 2b, d, and f). To evaluate the anteroposterior tortuosity of the retinal vein, we calculated the ratio ‘‘m/M’’. We also measured the inner vessel diameter of the retinal vein and artery using the Spectralis OCT method (Figure 2).14 The inner diameters of the retinal artery and retinal vein were measured at the AV crossing and 300 mm upstream from the AV crossing, respectively. The retinal artery and vein inner diameters were also averaged based on longitudinal and cross-sectional images (Figure 2). Independent observers measured m, M, and the inner vessel diameter. A blinded observer (TT) analyzed the data to determine the correlation between the tortuosity and the other parameters.
Statistical Analysis All data are expressed as the mean ± the standard error of the mean. The significance of differences in data between younger subjects and older subjects was determined with the Mann–Whitney U test. Commercially available software (SPSS v. 17.0J for Windows; SPSS Inc., Chicago, IL) was used for all
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FIGURE 1 Typical sectional OCT images of younger and older eyes. (a) OCT image of an eye from the group of younger subjects was obtained along the arrow A. (b) Longitudinal image of the vein along the arrow A. At the AV crossing point, the retinal vein ran beneath the retinal artery above the inner and outer segments of the retinal photoreceptors (IS/OS line) level. There was no venous narrowing at the AV crossing. (c) Sectional images of older eyes were also obtained along arrows A. (d) Longitudinal image of the vein at the AV crossing along arrow A. The retinal vein ran beneath the retinal artery to the IS/OS line level. There was no venous narrowing at the AV crossing.
statistical analyses. A p value of less than 0.05 was considered statistically significant.
RESULTS The patient characteristics are shown in Table 1. Mean age of the younger control subjects was 26.2 ± 2.9 years (range 21–30 years); the mean refractive error was 0.9 ± 1.2 D (range 2.00 to 0.25 D) and the mean axial length was 25.9 ± 2.4 mm. The mean age of the older subjects was 65.8 ± 4.8 years (range 61–73 years); the mean refractive error was 0.6 ± 1.3 D (range 2.50 to 1.25 D), and the mean axial length was 25.4 ± 2.1 mm. Among the 42 younger eyes, there were 82 firstorder and second-order AV crossings in the vascular arcade. A retinal artery was located anterior to the vein in 52 (n = 52) of the 82 AV crossings. Among the 48 older subject eyes, there were 93 AV crossings in the vascular arcade, and 59 artery-over-vein crossings. Representative images of younger and older eyes are shown in Figure 1(b) and (d) In 27 eyes (64.3 %) in younger subjects, the retinal vein was located above the inner and outer segments of the retinal photoreceptors (IS/OS line) level at the AV crossing
(Figure 1b). In contrast, in 30 eyes (66.7 %) in older subjects, the retinal vein ran beneath the retinal artery at the AV crossing (Figure 1d). There was no venous narrowing at the AV crossing in younger or older eyes (Figure 1b and d). In older subjects, mean m, M, m/M, artery inner diameter, and vein inner diameter were 76.5 ± 13.1 mm, 142.7 ± 21.2 mm, 0.52 ± 0.09, 89.2 ± 8.8 mm, and 112.9 ± 12.8 mm, respectively. In contrast, in younger subjects, mean m, M, m/M, artery inner diameter, and vein inner diameter were 64.1 ± 12.6 mm, 139.9 ± 22.4 mm, 0.46 ± 0.06, 88.6 ± 9.3 mm, and 115.1 ± 13.2 mm, respectively. The values of M and artery and vein inner diameters did not differ significantly between younger and older subjects. Both ‘‘m/M’’ and ‘‘m’’ were significantly (p = 0.021 and p = 0.018) lower in older subjects than in younger subjects (Figure 3).
DISCUSSION In the present study, the retinal vein at the AV crossing evaluated by vein depth measurement using HRA + OCT images was more curved anteroposteriorly in older eyes compared with younger eyes. Many studies have evaluated AV crossings Current Eye Research
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Tortuosity of the Retinal Vein at AV Crossings
FIGURE 2 OCT images of older eyes to evaluate the tortuosity of vein. (a) Sectional images of an eye from the group of older subjects were obtained along arrows, A, B, and C. (b) This image is the same as that in Figure 1(d). Hyper-reflective signs were observed at the top and bottom of the artery (black arrowhead). We measured ‘‘M’’, ‘‘m’’, vein diameter (Dv), and artery diameter (Da). (c) Crosssectional image of the retinal vein along arrow B, 300 mm away from the AV crossing. Hyper-reflective signs were observed at the top and bottom of the vein (black arrowhead). (d) This image is the same as that in Figure 2(c). We measured ‘‘M’’ and Dv at this point. (e) Cross-sectional images of the vein along arrow C at the AV crossing point. Hyper-reflective signs of the retinal vein were weak at the AV crossing. The IS/OS line was also weak because of the location of the above artery. (f) This image is the same as that in Figure 2(e). We measured ‘‘m’’ and Da here. Copyright ! 2015 Taylor & Francis Group, LLC
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FIGURE 3 Mean ‘‘m/M’’ of younger and older subjects. ‘‘m/M’’ was significantly decreased in older eyes compared with younger eyes. The bottom and the top of the box are the first and third quartiles, and the band inside the box is the median. The ends of the whiskers represent several possible alternative values. *p = 0.021 versus younger values.
histologically.8,9 Despite the importance of observing the morphologic features of vessels under physiologic conditions, such as blood flow, few studies have performed such precise evaluations. Some color fundus photograph studies have focused on AV crossings16 but AV crossings can only be observed horizontally on fundus photographs, and the retinal vein cannot be observed anteroposteriorly under the artery at the AV crossings. Conventional TD-OCT has a low resolution and it is thus difficult to assess the retinal structure precisely. The recently developed HRA + OCT is useful for noninvasive investigation of changes of the retinal structure because it has a higher resolution and faster scanning speed and image processing than the TDOCT.17,18 Muraoka et al.14,15,19 evaluated the anteroposterior tortuosity of the retinal vein in eyes with BRVO or central retinal vein occlusion with HRA + OCT images. They observed the anteroposterior tortuosity of the retinal vein at the AV crossing in healthy human eyes.19 There are no reports, however, of the extent of retinal vein tortuosity anteroposteriorly at the AV crossing in healthy eyes, especially in older subjects. Our findings support existing data indicating that the retinal vein runs deep under the artery and that the venous lumen is preserved at the AV crossing in normal eyes. In the present study, we were able to evaluate the anteroposterior tortuosity of the retinal vein at the AV crossing based on the ratio m/M determined from HRA + OCT images. There is no index for evaluating the anteroposterior tortuosity of the retinal vein. In the present study, we used m and M to calculate the ratio m/M as the extent of retinal vein tortuosity. In some older subjects, visualization of the junction between the IS/OS line was blocked by the retinal vein at the AV crossing (Figure 1d). In contrast, in all eyes of both older and
younger subjects, the RPE line was clearly observed at the AV crossing (Figure 1b and d). In addition, it was easy to detect the choroidal side outer hyper-reflective line of the retinal vein (Figure 1b and d). Therefore, m and M accurately represent the depth of the retinal vein. In this study, we used m/M as the index of the extent of retinal vein tortuosity. If all the retinal veins ran at a right angle to the artery at the AV crossing, the radius of the vein curvature might be the index of vein tortuosity. Retinal veins, however, cross the artery at various angles. When the angle of the AV crossing is small, the length of the vein under the artery is longer when it crosses at a right angle, and thus the radius of the vein curvature will be large. The index of the venous radius curvature was influenced by the angle of the AV crossing. Taken together, it is reasonable to assume that m/M represents the tortuosity of the retinal vein at the AV crossing. In the present study, we revealed for the first time that m/M was significantly smaller in older eyes than in younger eyes (Figure 3), suggesting that retinal veins are more curved at the AV crossing in older eyes than in younger eyes. This finding resulted from the significantly lower m in the older subjects (Table 1). The retinal vein ran deeper at the AV crossing point in older eyes than in younger eyes. We speculate that this might be due to increased arterial and venous wall thickness in older subjects, because there was no significant difference between the inner diameter of the artery or vein at the AV crossing in the two groups (Table 1). Michelson et al.20 reported that both arterial and venous vessel wall thicknesses, calculated as the difference in vessel diameter and flow diameter by scanning laser Doppler flowmetry, are increased by aging. Using the same method as in the present study, Muraoka et al.14 reported that both arterial and venous wall thicknesses positively correlated with age in eyes without hypertension. Based on these findings, we speculate that more thickened arterial and venous walls at the AV crossing in older eyes might lead to deeper veins in the retina at the AV crossing. The present study has some limitations. First, although HRA-OCT provides markedly clearer images than conventional OCT, we could not precisely measure the vein wall thickness at the AV crossing point, because it was difficult to determine the inner vein wall due to weakening of signal vein images by the above artery, especially in older eyes (Figure 2f). For the same reason, we were also unable to measure the inner diameter of the vein precisely at the AV crossing. Second, the result of the present study was influenced by arteriosclerosis to some extent, especially in the older subjects, because it is well known that arteriosclerosis is increased in older subjects. Some groups reported that arterial stiffness, evaluated by measuring the cardio-ankle vascular index, is increased by aging.21,22 Arteriosclerosis, however, cannot be excluded from the older group Current Eye Research
Tortuosity of the Retinal Vein at AV Crossings and thus it is inevitable that our result was affected by arteriosclerosis. Additional clinical studies are needed to evaluate the influences of arteriosclerosis on venous anteroposterior tortuosity. In conclusion, we measured the retinal vein depth and the arterial and venous inner diameter at the AV crossing using HRA-OCT and evaluated the anteroposterior tortuosity of the retinal vein by measuring the maximum and minimum retinal vein depths at the AV crossing. We found that venous anteroposterior tortuosity at the AV crossing increases with increased age.
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DECLARATION OF INTEREST The authors report that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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