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Year : 2017  |  Volume : 5  |  Issue : 1  |  Page : 17-22

Ocular hemodynamic alterations in patients of Type 2 diabetes mellitus

1 Department of Ophthalmology, NKP Salve Institute of Medical Sciences, Nagpur, Maharashtra, India
2 Department of Radio-Diagnosis, BJ Medical College and Sassoon Hospital, Pune, Maharashtra, India
3 Department of Radio-Diagnosis, Advanced Imaging Point, Nagpur, Maharashtra, India
4 NKP Salve Institute of Medical Sciences and Lata Mangeshkar Hospital, Nagpur, Maharashtra, India
5 MDS Bioanalytics, Nagpur, Maharashtra, India

Date of Submission16-Jul-2015
Date of Acceptance18-Jul-2016
Date of Web Publication6-Dec-2016

Correspondence Address:
Rekha R Khandelwal
Department of Ophthalmology, NKP Salve Institute of Medical Sciences, Nagpur - 440 022, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2320-3897.195304

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Purpose: To study ocular blood flow velocity in the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary artery in patients with Type 2 diabetes. Materials and Methods: The retrobulbar circulation in 46 eyes of Type 2 diabetic patients was compared with age-matched 21 nondiabetic eyes. The diabetic subjects were further divided into diabetics with no-clinical retinopathy (n = 24) and with either preproliferative or proliferative retinopathy (n = 22). Philips HD11XE machine was used for performing Color Doppler imaging. Results: The end-diastolic velocity (EDV) in OA was 3.21 cm/s in the preproliferative/proliferative group as compared to 6.0 and 8.5 cm/s in no-retinopathy and control group, respectively. The peak systemic velocities and EDVs of CRA in the diabetic group were significantly lower than those of normal subjects regardless of the retinopathy. The resistivity index (RI) of CRA was 0.81 in diabetic group and 0.70 in control group, which was statistically significant. Conclusion: The study showed reduced blood flow velocity and increased RI in Type 2 diabetic patients as compared to normal healthy individuals. There are significant changes noted in retrobulbar flow in patients with diabetic retinopathy as compared to patients without retinopathy.

Keywords: Color Doppler imaging, diabetic retinopathy, ocular hemodynamics, resistivity index, Type 2 diabetes mellitus

How to cite this article:
Khandelwal RR, Mundhada PA, Khandelwal RR, Majumdar M, Khandelwal RR, Raje D, Rathi A. Ocular hemodynamic alterations in patients of Type 2 diabetes mellitus. J Clin Ophthalmol Res 2017;5:17-22

How to cite this URL:
Khandelwal RR, Mundhada PA, Khandelwal RR, Majumdar M, Khandelwal RR, Raje D, Rathi A. Ocular hemodynamic alterations in patients of Type 2 diabetes mellitus. J Clin Ophthalmol Res [serial online] 2017 [cited 2022 Jun 27];5:17-22. Available from: https://www.jcor.in/text.asp?2017/5/1/17/195304

Diabetes affects around 347 million people worldwide, of which 37.7 million cases are estimated to be present in India. [1] The WHO divides diabetes into Type 1 (insulin-dependent) and Type 2 cases (noninsulin-dependent). Type 2 is an adult onset and more associated with diabetic retinopathy (DR). It is the leading cause of blindness in working population and it leads to severe social and occupational impairment. DR is due to long-term consequences of sustained hyperglycemia and is associated with genetic and systemic factors. DR is present in almost 20% of cases at the time of diagnosis. The incidence of DR is associated with duration of disease process. [2] Diabetes affects ocular circulation and altered ocular blood flow may contribute to the development and progression of DR. The exact nature of ocular blood flow abnormalities in diabetes has not yet been established, but increased resistance in peripheral vascular bed is noted even before the appearance of overt DR. [3],[4]

The recent advances in noninvasive imaging techniques such as Color Doppler imaging (CDI) have improved clinical evaluation of ocular hemodynamic circulation. It is a useful tool when standard diagnostic procedures are difficult in the presence of cataract or hazy media. [5] CDI has proved its usefulness in the other ocular conditions such as glaucoma, venous occlusion, age-related macular degeneration, and anterior ischemic optic neuropathy. [6],[7] The ophthalmic artery (OA), central retinal artery (CRA) and central retinal vein (CRV), posterior ciliary arteries (PCAs), and the superior ophthalmic vein can be easily identified using CDI. The circulatory parameters recorded include peak systolic velocity (PSV), end-diastolic velocity (EDV), and mean velocity (MV), the resistivity index (RI) and the pulsatility index. The purpose of this study was to measure blood flow velocity in the OA, CRA, and PCA in patients with Type 2 diabetes and compare the results with age-matched normal control subjects.

  Materials and Methods Top

In this nonrandomized comparative study, 46 Type 2 diabetic patients and 21 nondiabetic controls were included. The study was conducted at a rural-based hospital of Central India after approval by the Institutional Review Board. The diabetic subjects were recruited from the diabetic clinic and the nondiabetic healthy controls were enrolled from the hospital staff and voluntary workers. A single experienced ophthalmologist examined all the subjects. They underwent a thorough slit-lamp evaluation, intraocular pressure measurement by applanation tonometer, and dilated stereoscopic fundus examination with + 78 Diopter Volk lens. Patients with systemic hypertension (HT), renal disease, cardiac disease, or any other systemic illness complicating diabetes mellitus were excluded from the study. Patients with primary or secondary glaucoma, ocular inflammation, trauma, vascular disease (venous occlusion, nonarteretic ischemic optic neuropathy, etc.), and those who had undergone surgery or laser photocoagulation for DR were excluded from the study.

Diabetic patients were divided into no-DR (NDR) (retinopathy [−]) and DR groups (retinopathy [+]). NDR group had no clinical retinopathy or minimal changes of background DR (BDR). BDR was defined by the presence of microaneurysms, hemorrhages, and exudates. Patients with preproliferative DR (PPDR) and proliferative DR (PDR) were included in retinopathy group. PPDR comprised background changes plus two or more of the following: venous beading or reduplication, intraretinal microvascular abnormalities, deep intraretinal hemorrhages, and multiple cotton-wool spots. PDR was characterized by an area of papillary and/or epiretinal new vessel formation.

CDI was performed by a masked, experienced sonologist. Philips HD 11XE color doppler machine manufactured by Royal Philips Healthcare, 22100 (Bothell Everett Hwy, Bothell, WA 98021, United States) with 9-15 broadband MHz linear probe was used to perform CDI of the OA, CRA, and PCA. After the procedure was explained to the subjects, written consent was taken from all the participants. A 7.5 MHz probe was applied to the closed eyelids using sterile coupling gel in the supine position and fingers resting on the face to avoid probe pressure on the globe as shown in [Figure 1]. The identification of ocular vessels was done as per the anatomic location and flow characteristics, i.e., the arterial flow is pulsatile and is usually red (toward the probe) whereas venous flow has continuous spectrum and is blue (away from the probe). The anatomic location of ocular vessels (CRA, PCA) in a normal subject is shown in [Figure 2]. Examination was done in medium- to low-flow settings, and a sample volume of approximately 1.2 mm was chosen. The examination time for one eye was 10-15 min. Angle correction was applied to minimize errors in the measurement of the ocular blood flow. If the disease was symmetrical, then randomly one eye was chosen or the eye with more advanced disease was selected for the analysis. PSV and EDV of all three blood vessels mentioned above were obtained. RI was calculated according to Pourcelot's formula: RI = (PSV − EDV)/PSV.
Figure 1: Color Doppler imaging technique being done in a supine position

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Figure 2: Anatomic location of ocular vessels in a normal subject (CRA: central retinal artery, PCA: posterior ciliary artery, CRV: Central retinal vein, SOV: Superior ophthalmic vein)

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The MV velocities in OA, CRA, and PCA were compared across control group, diabetic group without retinopathy, and diabetic group with retinopathy using one-way ANOVA. Furthermore, RI was compared across these groups using one-way ANOVA. On observing the significance, pair-wise comparison of MVs, as well as RI, between groups was performed using Tukey's honest significant difference test. The significance was evaluated at 5% and the analysis was carried out in SPSS Inc. Released 2009. PASW Statistics for Windows, Version 18.0. Chicago: SPSS Inc.

  Results Top

There were 46 Type 2 diabetic and 21 normal subjects as shown in [Table 1]. Twenty-four subjects in diabetic group had no retinopathy or background changes (NDR/BDR) and were grouped as retinopathy (−) whereas 22 had PPDR/PDR and were grouped as retinopathy (+). There were four subjects with BDR, who were included in no retinopathy group. No statistical difference was found between the control group and retinopathy (−), as well as control and retinopathy (+), as regards age and gender.
Table 1: Demographic characteristics

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[Table 2] presents the MV of the OA and RIs in control and diabetic subjects. EDVs in diabetics, regardless of the presence or absence of retinopathy, were significantly lower than those of control subjects (P < 0.05). The RI in patients with DR (0.87 ± 0.04) was significantly greater (P < 0.05) than those in normal subjects (0.73 ± 0.06). The CDI of OA in normal and DR is shown in [Figure 3]a and b.
Figure 3: (a) Anatomic location of ophthalmic artery and its waveform in a normal subject. (b) Ophthalmic artery waveform in a patient of diabetic retinopathy

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Table 2: Ophthalmic artery blood flow velocities (cm/s) and resistivity indices in normal subjects and diabetic patients

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[Table 3] presents the MV of the CRA and RIs in normal and diabetic patients. The PSVs and EDVs in the diabetic group were significantly lower than those of normal subjects. A significant difference in EDV was found in the patients with and without retinopathy. The RI in patients with DR (0.83 ± 0.07) was significantly greater than control group (0.70 ± 0.12) and diabetic subjects without retinopathy (0.78 ± 0.06).
Table 3: Central retinal artery blood flow velocities (cm/s) and resistivity indices in normal subjects and diabetic patients

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[Table 4] presents the MV of PCA and RIs in control and diabetic patients. There was no significant difference in EDV of diabetic subjects without retinopathy as compared to control group; however, RI was significantly increased in diabetic patients with retinopathy (0.68 ± 0.09) as compared to those without retinopathy (0.51 ± 0.10).
Table 4: Posterior ciliary artery blood flow velocities (cm/s) and resistivity indices in normal subjects and diabetic patients

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  Discussion Top

CDI is a recent advance in ultrasonography which allows simultaneous two-dimensional imaging of structure and measurement of the blood flow with minimal discomfort and risk. Doppler spectral analysis allows quantitative assessment of blood flow velocity in the vessels. CDI is a useful tool for investigating the hemodynamic circulation in retro-orbital vessels. [8],[9] In diabetic patients when fundus evaluation and fluorescein angiography are difficult due to hazy media (vitreous hemorrhage or cataract), CDI can be used to evaluate ocular blood flow. Retina derives its main blood supply from the CRA, which is a branch of the internal carotid artery. [10],[11] PCA also supplies a part of retina and optic nerve. The blood flow velocity in CRA is pulsatile like OA. [12] Many studies have been reported on ocular circulation in diabetic patients using a variety of methods. Decreased blood flow velocity has been detected in the retinal circulation of the diabetic patients by blue-light entoptic measurement: scanning laser ophthalmoscopy and bidirectional laser Doppler. [13],[14],[15] There are even some reports suggesting increased ocular blood flow in the diabetic retina. These blood flow variations are due to other factors such as duration and type of diabetes, anatomic location of measurement, metabolic control, systemic diseases, and use of antihypertensive agents.

To the best of our knowledge, this is the first study on ocular blood flow in diabetics done on the Indian population. In total, 46 eyes of Type 2 diabetes mellitus patients were compared with 21 eyes of nondiabetic subjects.

In NDR/BDR group, we found EDVs of OA and CRA in diabetic subjects were significantly lower than those of normal subjects. The blood flow velocity in BDR is reported to be decreased in all three blood vessels, i.e., OA, CRA, and PCA. There are reports suggesting the blood flow velocity in the CRV to be increased in patients with BDR as compared to control group; however, in our study, we did not measure the flow of CRV. [16] We also found that the RI of OA was significantly greater in diabetic patients as compared to normal individuals even in the absence of retinopathy. These findings are comparable to the previous studies and show that hemodynamic disturbances in retrobulbar ocular circulation appear before clinical manifestations of DR. [9],[17],[18]

There are prospective studies done on diabetic patients and are reported in literature.

Sood et al. did a follow-up study for NPDR patients and reported an increase in RI in CRA and PCA as compared to baseline ocular blood flow parameters after 6 months. [19] Another prospective study reported that RI of CRA and PCA had increased in NPDR after 10 years of follow-up. [20] Both studies point toward significant changes in RI noted in CRA and PCA over time even without PPDR/PDR.

In the retinopathy group comprising the PPDR and PDR cases, blood flow velocities were found to be lower in OA, CRA, and PCA than those with NPDR/NDR group. The findings of the previously published studies indicate that the blood flow velocity in retrobulbar arteries decreases in eyes with DR and this decrease is more conspicuous in the CRA. Our findings are comparable to the earlier reports on PPDR and PDR. [21],[22] Of the 11 studies that used CDI to evaluate OA, five reported a lower blood velocity, five reported no change in velocity, and one reported high velocity in DR. [17]

We also found increased RI in PDR group, which was similar to the study done by Meng et al. [23]

Diabetic patients frequently have other noncommunicable diseases, which may alter ocular blood flow. Recently, many CDI studies are published on the correlation of DR with coronary artery disease. A study done by Krasnicki et al. reported that impaired blood flow found in OA and PCA in diabetic patients was not related to retinopathy but due to associated atherosclerosis in coronary arteries. He concluded that major ocular blood flow changes due to retinopathy are noted in CRA. [24] A study done by Fujioka et al. found a reduction in diastolic flow velocity in CRA in patients of DR with coronary artery disease. He summarized that this decrease could be due to decrease in cardiac output in coronary artery disease. [25] HT is considered to be a risk factor for the progression of DR. A recent article on ocular blood flow changes in patients with HT reported increased RI in PCA. [26]

Our study had several limitations as we have not excluded patients with coronary artery disease and HT. These might have altered the hemodynamic blood flow in retrobulbar circulation in diabetic patients. It is difficult to perform CDI study on a cohort of purely diabetic patients in developing countries like India because patients usually report in late stages of the DR. The study was done at a tertiary care setup with many rural patients visiting us. There were very few patients with BDR; most of them had PPDR. Hence, we included four such BDR cases in NDR group. Our study population was also relatively small. Therefore, the accuracy of differentiating between patients with and without retinopathy was relatively low. A large series might have disclosed additional features related to the CDI in diabetic and nondiabetic subjects. We recommend such study may be done in the family members of patients with PDR so that close follow-up can be done with CDI for a longer duration. We also advocate prospective, comparative studies to validate our results.

  Conclusion Top

Although it was a study with a small sample size, our results suggest that it has a potential to provide useful information related to altered ocular blood flow even before the appearance of DR. This also suggests CDI may have prognostic value in identifying those at risk of developing sight-threatening PDR.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Park K. Park's Textbook of Preventive and Social Medicine. 22 nd ed. Jabalpur, (M.P.): Banarasidas Bhanot Publishers; 2013. p. 363-4.  Back to cited text no. 1
Klein R, Klein BE, Moss SE, Davis MD, DeMets DL. The Wisconsin epidemiologic study: II prevalence and risk of diabetic retinopathy when age at diagnosis is thirty or more years. Arch Ophthalmol 1984;102:520-6.  Back to cited text no. 2
Guthoff RF, Berger RW, Winkler P, Helmke K, Chumbley LC. Doppler ultrasonography of the ophthalmic and central retinal vessels. Arch Ophthalmol 1991;109:532-6.  Back to cited text no. 3
Lieb WE, Cohen SM, Merton DA, Shields JA, Mitchell DG, Goldberg BB. Color Doppler imaging of the eye and orbit. Technique and normal vascular anatomy. Arch Ophthalmol 1991;109:527-31.  Back to cited text no. 4
Goebel W, Lieb WE, Ho A, Sergott RC, Farhoumand R, Grehn F. Color Doppler imaging: A new technique to assess orbital blood flow in patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 1995;36:864-70.  Back to cited text no. 5
Plange N, Kaup M, Weber A, Harris A, Arend KO, Remky A. Performance of colour Doppler imaging discriminating normal tension glaucoma from healthy eyes. Eye (Lond) 2009;23:164-70.  Back to cited text no. 6
Kaup M, Plange N, Arend KO, Remky A. Retrobulbar haemodynamics in non-arteritic anterior ischaemic optic neuropathy. Br J Ophthalmol 2006;90:1350-3.  Back to cited text no. 7
Lieb WE. Color Doppler ultrasonography of the eye and orbit. Curr Opin Ophthalmol 1993;4:68-75.  Back to cited text no. 8
Arai T, Numata K, Tanaka K, Kiba T, Kawasaki S, Saito T, et al. Ocular arterial flow hemodynamics in patients with diabetes mellitus. J Ultrasound Med 1998;17:675-81.  Back to cited text no. 9
Karadeniz-Bilgili MY, Ekmekci Y, Koksal A, Akarsu C, Ziraman I. Effects of hypertension and antihypertensive treatment on retrobulbar circulation detected on Doppler sonography. J Ultrasound Med 2004;23:13-7.  Back to cited text no. 10
Hayreh SS, Dass R. The ophthalmic artery: II. Intra-orbital course. Br J Ophthalmol 1962;46:165-85.  Back to cited text no. 11
Steigerwalt RD Jr., Belcaro GV, Laurora G, Cesarone MR, De Sanctis MT, Incandela L. Ocular and orbital blood flow in patients with essential hypertension treated with trandolapril. Retina 1998;18:539-45.  Back to cited text no. 12
Grunwald JE, Riva CE, Sinclair SH, Brucker AJ, Petrig BL. Laser Doppler velocimetry study of retinal circulation in diabetes mellitus. Arch Ophthalmol 1986;104:991-6.  Back to cited text no. 13
Rimmer T, Fallon TJ, Kohner EM. Long-term follow-up of retinal blood flow in diabetes using the blue light entoptic phenomenon. Br J Ophthalmol 1989;73:1-5.  Back to cited text no. 14
Wolf S, Arend O, Toonen H, Bertram B, Jung F, Reim M. Retinal capillary blood flow measurement with a scanning laser ophthalmoscope. Preliminary results. Ophthalmology 1991;98:996-1000.  Back to cited text no. 15
Dimitrova G, Kato S, Tamaki Y, Yamashita H, Nagahara M, Sakurai M, et al. Choroidal circulation in diabetic patients. Eye (Lond) 2001;15(Pt 5):602-7.  Back to cited text no. 16
Dimitrova G, Kato S. Color Doppler imaging of retinal diseases. Surv Ophthalmol 2010;55:193-214.  Back to cited text no. 17
Evans DW, Harris A, Danis RP, Arend O, Martin BJ. Altered retrobulbar vascular reactivity in early diabetic retinopathy. Br J Ophthalmol 1997;81:279-82.  Back to cited text no. 18
Sood S, Narang S, Kocchhar S, Sarda S, Aggarwal S, Arya SK. Correlation of progression of diabetic retinopathy with the alterations in retrobulbar circulation. Nepal J Ophthalmol 2013;5:147-53.  Back to cited text no. 19
Neudorfer M, Kessner R, Goldenberg D, Lavie A, Kessler A. Retrobulbar blood flow changes in eyes with diabetic retinopathy: A 10-year follow-up study. Clin Ophthalmol 2014;8:2325-32.  Back to cited text no. 20
MacKinnon JR, McKillop G, O'Brien C, Swa K, Butt Z, Nelson P. Color Doppler imaging of the ocular circulation in diabetic retinopathy. Acta Ophthalmol Scand 1997;75:386-9.  Back to cited text no. 21
Mendívil A, Cuartero V, Mendívil MP. Ocular blood flow velocities in patients with proliferative diabetic retinopathy and healthy volunteers: A prospective study. Br J Ophthalmol 1995;79:413-6.  Back to cited text no. 22
Meng N, Liu J, Zhang Y, Ma J, Li H, Qu Y. Color Doppler imaging analysis of retrobulbar blood flow velocities in diabetic patients without or with retinopathy: A meta-analysis. J Ultrasound Med 2014;33:1381-9.  Back to cited text no. 23
Krasnicki P, Dmuchowska DA, Proniewska-Skretek E, Dobrzycki S, Mariak Z. Ocular haemodynamics in patients with type 2 diabetes and coronary artery disease. Br J Ophthalmol 2014;98:675-8.  Back to cited text no. 24
Fujioka S, Karashima K, Nishikawa N, Saito Y. Ocular circulation in diabetic patients with coronary artery disease. Graefes Arch Clin Exp Ophthalmol 2006;244:163-9.  Back to cited text no. 25
Akal A, Ulas T, Goncu T, Karakas E, Karakas O, Kurnaz F, et al. Evaluation of resistive index using color Doppler imaging of orbital arteries in geriatric patients with hypertension. Indian J Ophthalmol 2014;62:671-4.  Back to cited text no. 26
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