|Year : 2022 | Volume
| Issue : 3 | Page : 254-258
Choroidal thickness and choroidal vascularity index in diabetic retinopathy and diabetic macular edema – A clinical study
Sozhamadevi Subramaniyan, Venkatesh Perumal, Jaya Prabha Balachandar
Department of Ophthalmology, Government Mohan Kumaramangalam Medical College Hospital, Salem, Tamil Nadu, India
|Date of Submission||06-Feb-2022|
|Date of Decision||06-Jul-2022|
|Date of Acceptance||08-Jul-2022|
|Date of Web Publication||26-Sep-2022|
94/24, Sundar Gardens, Modern Theatres Premises, Salem, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Purpose: To evaluate the choroidal thickness and choroidal vascularity index (CVI) in various stages of diabetic retinopathy and to assess its significance in diabetic macular edema. Materials and Methods: 166 eyes of 83 patients were evaluated in this study. 116 eyes were with various stages of diabetic retinopathy and 50 eyes were non-diabetic healthy controls. Spectral Domain Optical Coherence Tomography (SD OCT) was done for all patients. The choroidal thickness and the macular thickness at the fovea, 500 μm nasal, temporal, superior and inferior to the fovea were measured manually, and CVI was calculated as the ratio between the total choroidal area and the luminal area using ImageJ software. Results: The mean age of the study group was 55.95 ± 10.57 years and that of the control group was 53.33 ± 11.28 years. The choroidal thickness was significantly decreased in patients with proliferative diabetic retinopathy (p < 0.005). CVI was inversely proportional to the severity of diabetic retinopathy and was statistically significant (p < 0.01 to 0.005). In eyes with DR and macular edema a significant decrease in choroidal thickness (p = 0.019) was observed; however, the decrease in CVI was not significant (p = 0.056). Conclusion: In diabetic retinopathy, the choriodal thickness and CVI decreases as the severity of the retinopathy increases. Choroid plays an important role in disease progression. But in eyes with diabetic retinopathy associated with or without macular edema, there is no significant difference in CVI.
Keywords: Choroidal thickness, choroidal vascularity index, diabetic retinopathy
|How to cite this article:|
Subramaniyan S, Perumal V, Balachandar JP. Choroidal thickness and choroidal vascularity index in diabetic retinopathy and diabetic macular edema – A clinical study. TNOA J Ophthalmic Sci Res 2022;60:254-8
|How to cite this URL:|
Subramaniyan S, Perumal V, Balachandar JP. Choroidal thickness and choroidal vascularity index in diabetic retinopathy and diabetic macular edema – A clinical study. TNOA J Ophthalmic Sci Res [serial online] 2022 [cited 2022 Nov 30];60:254-8. Available from: https://www.tnoajosr.com/text.asp?2022/60/3/254/357111
| Introduction|| |
Diabetic retinopathy is one of the most common causes of vision loss worldwide and is showing an increasing trend. It is the leading cause of legal blindness among working age group adults. Diabetes mellitus affects all small and large blood vessels in the body and results in tissue injury and degeneration. In the eye, the focus has always been on the retinal changes, though 85% of the blood supply to the eye is in the choroidal vasculature. Choroidal vasculature supplies oxygen and nutrients to the outer retina. The decrease in oxygenation in choroidal vasculature may be the reason for the loss of cones leading to retinal dysfunction in diabetics even when no retinopathy is present.,
The vascular changes in the choroid secondary to diabetes are increased vascular tortuosity, vascular outpouchings, microaneurysms, nonperfusion areas, vascular dilations, vascular narrowing and choroidal neovascularisation and these are similar to the retinal changes. These alterations in choroidal vasculature compromise the blood-retina barrier and play a critical role in the pathophysiology of the disease called diabetic choroidopathy. Before the advent of Optical Coherence Tomography (OCT), choroid was evaluated by indocyanine green angiography, laser Doppler flowmetry and B scan ultrasonography. Spectral Domain OCT (SD-OCT) offers high resolution cross sectional images of retina and choroid that helps in studying choroidal pathology in detail.
The role of choroid in diabetic retinopathy has been evaluated by studying the choroidal thickness. Previous studies on choroidal thickness have shown contradicting results on the thickness of choroid in relation to the severity of diabetic retinopathy.,,,,,, Studies by Vujosevic et al. Regatieri et al., Unsal E et al. and Sudhalkar et al. showed decrease in Choroidal thickness (CT) in diabetic retinopathy. In contrast, Xu J et al. showed no association between CT and severity of diabetic retinopathy. Kim et al. concluded CT increased significantly as the severity of diabetic retinopathy increased.
Choroidal vascularity index (CVI) is a novel tool for measuring and quantifying both luminal and stromal components. It is the ratio between luminal choroidal area (LCA) and total choroidal area (TCA). CVI gives an indirect measure and a better assessment of choroidal vascularity.,
In this study, choroidal thickness and CVI at the macula was evaluated in all stages of diabetic retinopathy. This was compared with the control group and its relationship with diabetic macular edema was also assessed.
| Materials and Methods|| |
In this prospective observational study, 166 eyes of 83 patients were included in this study. Of these, 116 eyes were with various stages of diabetic retinopathy and 50 eyes were healthy controls without diabetes. Patients with high refractive errors, opaque media, previous ocular surgeries, age related macular degeneration, arterial and vein occlusions, hypertensive retinopathy, glaucoma and other ocular and retinal pathology and other systemic diseases were excluded from this study. DR patients undergoing and undergone laser photocoagulation and intravitreal anti-VEGF were also excluded from the study.
This study was approved by the institutional ethical committee and informed consent was obtained from all the patients.
All patients were examined for Best Corrected Visual Acuity, Anterior segment examination by Slit lamp biomicroscopy, intraocular pressure measurement by Goldmann applanation tonometer. Detailed history of systemic illness, duration of diabetes and treatment details was obtained. After pupillary dilatation, fundus examination was done by direct ophthalmoscopy and slit lamp biomicroscopy with 90D lens. A single investigator classified Diabetic Retinopathy as per Early Treatment Diabetic Retinopathy Study (ETDRS) classification. SD OCT was taken with Radial and line protocol scans using TOPCON 3D OCT Maestro 2. Choroidal thickness was measured from the outer border of the retinal pigment epithelium to the inner scleral border at the fovea, 500 μm superior, 500 μm inferior, 500 μm nasal and 500 μm temporal to the fovea. [Figure 1] Macular thickness was measured from the outer border of the retinal pigment epithelium to the internal limiting membrane at the vitreoretinal interface.
CVI was calculated using ImageJ software. Polygon sections tool was used to select the choroidal area. It was marked along the Choroidal-RPE junction and the sclerochoroidal junction and TCA was marked. After adjusting the brightness, the image was converted to 8-bit image and binarisation was done using Niblack autolocal threshold. LCA was calculated by selecting the dark pixels in the image. CVI is the ratio between LCA and TCA. [Figure 2] The choroidal thickness and CVI measurement was done manually by the second investigator.
|Figure 2: Choroidal vascularity index (CVI) calculation using ImageJ software|
Click here to view
The collected data were analysed with IBM.SPSS statistics software 23.0 Version. To describe about the data descriptive statistics mean and S.D were used. To find the significant difference between choroidal thickness and CVI among different groups in the multivariate analysis the one way ANOVA with Tukey's Post-Hoc test was used. As a single investigator measured CVI and CT inter-observer variation was not tested. To assess the relationship of macular thickness with choroidal thickness and CVI, Pearson's correlation was used with a confidence interval of 95. In both the above statistical tools, the probability value of 0.05 is considered as significant level.
| Results|| |
The mean age of the study group was 55.31 ± 10.89 years. The mean age of different groups was also calculated. Student's t test was used to assess the statistical difference. There was no statistical difference between the mean ages of different groups [Table 1].
The mean choroidal thickness in control group was 282.93 ± 30.23 μm. There was an increase in choroidal thickness in mild NPDR (304.07 ± 30.86 μm). However, it was not significant. There was a progressive decrease in choroidal thickness as the severity increased. The mean CT in moderate NPDR was 281.11 ± 64.24 μm and in severe NPDR was 277.57 ± 40.85 μm. But it was not statistically significant (p > 0.05). The mean CT in PDR was 230.60 ± 32.26 μm and found to be significantly decreased [Table 2].
|Table 2: Choroidal thickness and choroidal vascularity index in different stages of diabetic retinopathy|
Click here to view
The CVI showed a progressive decrease as the severity of the retinopathy increased. The mean CVI in the control group was 66.85 ± 2.36. In patients with mild NPDR it was 64.13 ± 2.27. This was a significant decrease when compared to control group. In eyes of moderate NPDR, severe NPDR and PDR, the CVI was 61.41 ± 2.79, 60.98 ± 5.01 and 59.49 ± 3.17, respectively. These were highly significant when compared to control group [Table 2].
There was a significant negative correlation between the macular thickness and choroidal thickness in diabetic retinopathy without macular edema (284.63 ± 26.80 μm) and highly significant negative correlation in diabetic retinopathy with macular edema (392.18 ± 91.71 μm). On comparing macular thickness and CVI in all stages of diabetic retinopathy, there was no significant correlation [Table 3].
|Table 3: Correlation of Diabetic macular edema with choroidal thickness and choroidal vascularity index|
Click here to view
There was no significant decrease in CVI between eyes with diabetic macular edema and without diabetic macular edema. But there was a significant decrease in choroidal thickness in eyes with diabetic macular edema when compared to eyes without diabetic macular edema (p = 0.019) and control (0.0005) [Table 4].
|Table 4: Choroidal thickness and choroidal vascularity index in eyes with diabetic macular edema|
Click here to view
| Discussion|| |
The choroid consists of blood vessels, collagenous and elastic connective tissue, melanocytes, fibroblasts and immune cells. Majority of the choroid is formed by blood vessels and is divided into Haller's layer, Sattler's layer and choriocapillaries and contribute to the thickness of the choroid.
Diabetes affects all the blood vessels in the body. The focus of vascular changes has always been on the retinal vessels, but choroidal vessels are also similarly affected as the retinal vessels. A study on vascular changes in the eye has shown changes like loss of choriocapillaries, luminal narrowing, and thickening of basement membranes, large and intermediate blood vessel tortuosity, vascular hypercellularity and microaneurysms. These changes in the choroid correlated with the severity of the diabetes and glycemic control. Doppler studies on the choroidal vasculature also showed decreased choroidal blood flow in patients with diabetic retinopathy.,
In this study there was an increase in choroidal thickness in diabetic patients without retinopathy and mild NPDR. However this was not significant. This may be due to the inflammatory pathology in the initial stages of DR. In moderate NPDR to PDR, there was a progressive decrease in CT and the decrease was significant in patients with PDR [Table 2] and [Graph 1].
Regatieri et al. in their study showed that the subfoveal choroid was thinner in patients with nonproliferative diabetic retinopathy, diabetic macular edema and treated proliferative diabetic retinopathy. Unsal E et al. and Sudhalkar et al. found that CT decreases as the disease progresses from mild–moderate NPDR to PDR and in DME. Vujosevic et al. also reported that the mean subfoveal CT decreased significantly with increasing level of diabetic retinopathy and no significant difference between controls and diabetic patients without detectable diabetic retinopathy. In contrast, Xu J et al. in their study concluded that patients with diabetes mellitus had thicker subfoveal choroid and there is no association between CT and the presence and severity of diabetic retinopathy. Kim et al. also in their study concluded that CT increased significantly as the severity of diabetic retinopathy. But also there was a decrease in CT after pan retinal photocoagulation.
CVI is a better parameter in evaluating the choroidal pathology as it has lesser variability and less influence from other physiological factors when compared to choroidal thickness. In this study, a significant decrease in CVI was observed as the severity of the disease progressed from mild NPDR to PDR. Also CVI (65.14 ± 3.77) was decreased in patients with diabetes with no retinal abnormalities compared to control group (66.85 ± 2.36). But this was not significant [Table 2] and [Graph 2].
Kim M et al. and Aksoy M et al. in their study reported significant decrease in CVI with increase in severity of diabetic retinopathy. Foo VHX et al. in their study concluded that CVI was lower in diabetic patients and correspond with the duration of the disease irrespective of glycemic control and affects the large vessels before the medium-sized vessels.
In DME, there was no correlation between macular thickness and CVI in our study. However, the CT decreased as the macular thickness increased (macular edema) and it was statistically significant. But, Kim et al. and Endo et al. in their studies showed that choroid is thicker in diabetic retinopathy patients with DME than in patients without DME.
On comparing eyes with diabetic retinopathy with DME and without DME, there was a decrease in CVI clinically but it was not significant statistically. Decrease in CVI is due to microangiopathic changes in choroid. It starts to manifest in very early stage of diabetic retinopathy and hence there is no significant change when DR is associated with DME.
| Conclusion|| |
The choriodal thickness and CVI decrease as the severity of the retinopathy increases. Of the two, the CVI is a better indicator of the disease progression.
The choriodal thickness and CVI are not altered significantly in eyes with diabetic retinopathy with diabetic macular edema.
The changes in diabetic retinopathy are not only due to changes in retinal vasculature but also due to the changes in the choroid.
The vascular supply for outer retina is from choroidal vasculature. Assessing choroidal vascularity index (CVI) could be an early predictor of diabetic retinopathy even before clinical manifestations are seen. In diabetic patients, CVI was found to decrease with severity of retinopathy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Klein BEK. Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol 2007;14:179-83.
Lovasik J, Kergoat H. Electroretinographic results and ocular vascular perfusion in type I diabetes. Invest Ophthalmol Vis Sci 1993;34:1731-43.
Holopigian K, Greenstein VC, Seiple W, Hood DC, Carr RE. Evidence for photoreceptor changes in patients with diabetic retinopathy. Invest Ophthalmol Vis Sci 1997;38:2355-65.
Lutty GA. Diabetic choroidopathy. Vis Res 2017;139:161-7.
Xu J, Xu L, Du K, Shao L, Chen C, Zhou J, et al
. Subfoveal choroidal thickness in diabetes and diabetic retinopathy. Ophthalmology 2013;120:2023-8.
Kim J, Lee D, Joe S, Kim J, Yoon Y. Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 2013;54:3378-84.
Querques G, Lattanzio R, Querques L, Del Turco C, Forte R, Pierro L, et al
. Enhanced depth imaging optical coherence tomography in type 2 diabetes. Invest Ophthalmol Vis Sci 2012;53:6017-24.
Vujosevic S, Martini F, Cavarzeran F, Pilotto E, Midena E. Macular and peripapillarychoroidal thickness in diabetic patients. Retina 2012;32:1781-90.
Lee H, Lim J, Shin M. Comparison of choroidal thickness in patients with diabetes by spectral-domain optical coherence tomography. Korean J Ophthalmol 2013;27:433-9.
Regatieri C, Branchini L, Carmody J, Fujimoto J, Duker J. Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina 2012;32:563-8.
Adhi M, Brewer E, Waheed N, Duker J. Analysis ofmorphological features and vascular layers of choroid indiabetic retinopathy using spectral-domain optical coherence tomography. JAMA Ophthalmol 2013;131:1267-74.
Unsal E, Eltutar K, Zirtiloğlu S, Dinçer N, OzdoğanErkul S, Güngel H. Choroidal thickness in patients with diabetic retinopathy. Clin Ophthalmol 2014;8:637-42.
Sudhalkar A, Chhablani JK, Venkata A, Raman R, Rao PS, Jonnadula GB. Choroidal thickness in diabetic patients of Indian ethnicity. Indian J Ophthalmol 2015;63:912-6.
] [Full text]
Agrawal R, Gupta P, Tan KA, Cheung CM, Wong TY, Cheng CY. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study. Sci Rep 2016;6:21090. doi: 10.1038/srep21090.
Tan KA, Laude A, Yip V, Loo E, Wong EP, Agrawal R. Choroidal vascularity index-a novel optical coherence tomography parameter for disease monitoring in diabetes mellitus? Acta Ophthalmol 2016;94e612-6.
Weinberger D, Kramer M, Priel E, Gaton DD, Axer-siegel R, Yassur Y. Indocyanine green angiographic findings in nonproliferative diabetic retinopathy. Am J Ophthalmol 1998;126:238-47.
Mrejen S, Spaide RF. Optical coherence tomography: Imaging of the choroid and beyond. Surv Ophthalmol 2013;58:387-429.
Kim M, Ha MJ, Choi SY, Park YH. Choroidal vascularity index in type-2 diabetes analyzed by swept-source optical coherence tomography. Sci Rep 2018;8:70. doi: 10.1038/s41598-017-18511-7.
Aksoy M, Simsek M, Apaydın M. Choroidal vascularity index in patients with type1 diabetes mellitus without diabetic retinopathy. Curr Eye Res 2021;46:865-70.
Foo VHX, Gupta P, Nguyen QD, Chong CCY, Agrawal R, Cheng CY, et al
. Decrease in choroidal vascularity index of Haller's layer in diabetic eyes precedes retinopathy BMJ Open Diabetes Res Care 2020;8:e001295. doi: 10.1136/bmjdrc2020001295.
Endo H, Kase S, Takahashi M, Saito M, Yokoi M, Sugawara C, et al
. Relationship between diabetic macular edema and choroidal layer thickness. PLoS One 2020;15:e0226630. doi: 10.1371/journal.pone. 0226630.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]