|Year : 2017 | Volume
| Issue : 2 | Page : 532-537
Sub foveal choroidal thickness by enhanced depth imaging optical coherence tomography in type II diabetes mellitus
Hatem M Marey1, Sameh M Elgouhary1, Ahmed A Gad El Rab2
1 Department of Ophthalmology, Menoufia University, Shebeen El-Kom, Egypt
2 Embaba Ophthalmic Hospital, Giza, Egypt
|Date of Submission||23-Aug-2016|
|Date of Acceptance||25-Oct-2016|
|Date of Web Publication||25-Sep-2017|
Ahmed A Gad El Rab
Embaba Ophthalmic Hospital, Giza, 12651
Source of Support: None, Conflict of Interest: None
To evaluate the subfoveal choroidal thickness (ChT) in type II diabetes mellitus (DM) using enhanced depth imaging optical coherence tomography (EDI-OCT).
Diabetic retinopathy (DR) is because of hemodynamic abnormalities. The choroid provides oxygen and nutrients to the outer retina. EDI-OCT can image the choroid in vivo.
Patients and methods
A prospective clinical randomized study was carried out focusing on 100 eyes of 100 patients divided into two groups: group A included 50 eyes of 50 diabetic patients with type II DM (20–50 years) and group B included 50 eyes of 50 age-matched normal healthy controls with no sex or laterality specification. The subfoveal ChT, using EDI-OCT, was measured from the posterior edge of retinal pigment epithelium to the choroioscleral junction.
The mean age of the patients was 42 ± 7 and 39 ± 9 years in group A and B, respectively. The mean DM duration in group A was 7.96 ± 3.9 years. Subfoveal ChT was found to be 291 ± 42 μm in group A [275.31 ± 31 μm for no apparent retinopathy (no DR), 298 ± 42 μm for nonproliferative diabetic retinopathy, 309 ± 58 μm for proliferative diabetic retinopathy, 277 ± 29 μm for diabetic macular edema (DME) absent, and 306 ± 47 μm for DME present], whereas it was 284 ± 54 μm in group B. There was a statistically significant positive correlation between subfoveal ChT and DM duration (P = 0.00).
Subfoveal ChT was found to be correlated with the stage of DR. Progressive thickening of the choroid with the progression of DR and/or the development of DME may reflect the concurrent progression of diabetic choroidopathy.
Keywords: choroidal thickness, diabetic retinopathy, enhanced depth imaging optical coherence tomography, type II diabetes mellitus
|How to cite this article:|
Marey HM, Elgouhary SM, Gad El Rab AA. Sub foveal choroidal thickness by enhanced depth imaging optical coherence tomography in type II diabetes mellitus. Menoufia Med J 2017;30:532-7
|How to cite this URL:|
Marey HM, Elgouhary SM, Gad El Rab AA. Sub foveal choroidal thickness by enhanced depth imaging optical coherence tomography in type II diabetes mellitus. Menoufia Med J [serial online] 2017 [cited 2019 Aug 19];30:532-7. Available from: http://www.mmj.eg.net/text.asp?2017/30/2/532/215464
| Introduction|| |
Diabetic retinopathy (DR) is because of the breakdown of retinal vasculature integrity and hemodynamic abnormalities . Doppler flowmetry studies indicated that the choroidal blood flow may decrease in the early stage of DR and decrease further in the presence of macular edema .
The choroidal vasculature, especially the choriocapillaris, provides oxygen and nutrients to the outer retina and is responsible for maintaining the highly metabolically active photoreceptor cells . As there is no retinal vasculature in the foveal region, impairment of the choriocapillaris may cause severe functional damage to the retinal tissue in the fovea. Therefore, in-vivo evaluation of the structural changes in the choroid might be very insightful to determine the pathogenesis of the progression of the macular changes in diabetic eyes. Diabetic retinopathy may cause atrophy of the choriocapillaris endothelium as evidenced by histologic studies . There are few clinical studies on choroidal angiopathy in DM; this is because of the difficulty of imaging the choroid in vivo .
Spectral-domain optical coherence tomography (SD-OCT) technology improves the scan resolution; it shows bands that seem to correspond to the anatomic layers of the human retina and enables visualization of even small retinal details of the photoreceptor layer, such as the inner segment/outer segment junction. Recently, a new approach to improve depth imaging by OCT, termed enhanced depth imaging (EDI-OCT), has been shown to be able to reliably image the full thickness of the choroid. EDI-OCT uses SD-OCT equipment (Spectralis SD-OCT). In this manner, EDI-OCT may represent a useful approach to investigate, in vivo, the choroidal changes in diabetic eyes with or without diabetic retinopathy .
In this study, using EDI-OCT, we evaluated the subfoveal choroidal thickness (ChT) in the eyes of type II DM patients.
| Patients and Methods|| |
This is a prospective clinical randomized study carried out at Embaba Ophthalmic Hospital, Giza Medical Directory, Ministry of Health and the Department of Ophthalmology, Menoufia University, Egypt, between August 2014 and August 2015. This study was approved by the clinical research committee of the Menoufia University Hospital and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from each participant. This study focused on 100 eyes of 100 patients divided into two groups: group A included 50 eyes of 50 diabetic patients with type II DM (20–50 years) and group B included 50 eyes of 50 age-matched normal healthy controls with no sex or laterality specification. Only one eye from each participant was randomly selected as the study eye for analysis. The participants were recruited from among attendants seeking ophthalmic services at Ophthalmology Clinics of Menoufia University and Embaba Ophthalmic Hospitals. Exclusion criteria included participants with medical problems causing diminution of vision other than DM, such as media opacity obscuring fundus view (dense cataract or vitreous hemorrhage), systemic hypertension, glaucoma, hyperopia of +3 diopters (D) or more, myopia of −6 D or more, any macular abnormalities such as choroidal neovascularization, asymptomatic pigment epithelial detachment, age-related macular degeneration, intraocular surgery (except for cataract), and treatment for DR in the form of laser treatment or intravitreal injection.
The participants underwent assessment of medical history including duration of DM, uncorrected and best-corrected visual acuity using the Snellen chart in decimals, intraocular pressure measurement using a Goldmann applanation tonometer, and anterior segment and fundus examination by slit-lamp biomicroscopy. Diabetic eyes were graded according to the Early Treatment Diabetic Retinopathy Study as follows: no apparent retinopathy (no DR), nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Diabetic macular edema (DME) was grouped into DME absent and DME present.
Acquisition of the choroidal image was performed in all participants in the EDI mode of the Spectralis SD-OCT device (software, version 184.108.40.206; Heidelberg Engineering, Dossenheim, Germany).
The EDI-OCT scans were captured by a single operator (AA) using the Spectralis EDI mode, a preset software-driven algorithm that places the retinal pigment epithelium near the zero-delay line while producing an upright enhanced choroidal image.
Each OCT scan was centered on the patient's fixation, which was verified to correspond to the center of the fovea.
The EDI-OCT scans were viewed and measured manually using a special caliper ruler incorporated into the Spectralis software. The ChT was measured at the fovea from the outer border of the hyper-reflective line corresponding to the retinal pigment epithelium–Bruch's membrane complex to the hyporeflective line or margin corresponding to the chorioscleral interface [Figure 1] and [Figure 2].
|Figure 1: Representative scan for choroidal thickness segmentation and measurement, case from group B.|
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|Figure 2: Representative scan for choroidal thickness segmentation and measurement, case from group A.|
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Statistical analysis was carried out on the IBM SPSS software, version 21.0 (SPSS Inc., Chicago, Illinois, USA). The independent t-test data analysis was carried out to test for differences in numerical variables between the two groups and the c2-test was used for non-numerical variables. Data were expressed as mean ± SD. Pearson's correlation was used for correlating both age and duration of DM with central conduction time. A 95% confidence interval and a 5% level of significance were adopted; therefore, the results with a P value 0.05 or less were considered significant.
| Results|| |
The participants in group A, with a duration of diabetes of 7.96 ± 3.9 (1–15) years, were subcategorized as follows: 22 (44%) women and 28 (56%) men; 21 (42%) right eyes and 29 (58%) left eyes; 16 (32%) eyes with no DR, 28 (56%) eyes with NPDR and six (12%) eyes with PDR; and 26 (52%) eyes with DME present and 24 (48%) eyes with DME absent. The participants in group B were subcategorized as follows: 20 (40%) women and 30 (60%) men; and 19 (38%) right eyes and 31 (62%) left eyes [Table 1].
The subfoveal ChT was found to be 291 ± 42 μm (225–401 μm) in group A and 283 ± 54 μm (166–368 μm) in group B. There was a statistically nonsignificant difference in the ChT (P = 0.39), independent t-test [Table 2].
|Table 2: Differences in the subfoveal choroidal thickness of the groups studied|
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On comparing the grade of DR with the subfoveal ChT in both groups, a statistically nonsignificant difference was found in subfoveal ChT in no DR, NPDR, and PDR compared with the healthy controls (P = 0.56, 0.23, and 0.28, respectively). A statistically nonsignificant difference in subfoveal ChT was found in group A with DME absent and DME present compared with group B (P = 0.08 and 0.57, respectively) [Table 3].
|Table 3: Difference in the Subfoveal choroidal thickness among diabetics of different sub groups and healthy controls|
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There was a nonsignificant difference in the subfoveal ChT in group A in relation to sex and laterality of the eye examined compared with group B (P = 0.14 for women, 0.43 for men, 0.78 for the right eye, and 0.60 for the left eye) [Table 4].
|Table 4: Differences in the subfoveal choroidal thickness of the groups studied in relation sex and laterality|
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On correlating the DM duration with the subfoveal ChT, as statistically significant positive correlation (increase in ChT with increase of diabetic duration) (P = 0.00) was found. Correlation of the age of participants with the subfoveal ChT showed a statistically significantly positive correlation in group A (increase in ChT with increase in age) and a statistically significantly inverse correlation in group B (decrease in ChT with increase in age) (P = 0.00 and 0.02) [Table 5].
|Table 5: Correlation between age and duration of diabetes mellitus in the subfoveal choroidal thickness|
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| Discussion|| |
Diabetic retinopathy is a well-documented sight-threatening complication of DM because of the breakdown of retinal vasculature integrity and hemodynamic abnormalities, and despite the fact that DM affects the choroid, little is known clinically about diabetic choroidopathy; also, a structurally and functionally normal choroidal vasculature is essential for normal retinal function. Hence, an abnormal choroidal blood volume and/or compromised flow can result in photoreceptor dysfunction and death . Studies using indocyanine green angiography show filling delay or defects in the choriocapillaris, microaneurysms, saccular dilatations in the choriocapillaris, and choroidal neovascularization in diabetics .
A limited number of noninvasive imaging techniques are available for assessment of the choroid; the introduction of OCT enables further objective evaluation of DR. The EDI-OCT has provided the advantage of in-vivo cross-sectional imaging of the choroid, similar to the retina, with standard commercially available spectral-domain OCT machines . In this study, we reviewed this imaging technique to evaluate the subfoveal ChT in diabetic eyes.
One hundred ART scans per se ction are often used for a good image quality, and the patient must be able to fixate well during image acquisition, which may not be possible sometimes, but the Best et al.  study noted that measurement of ChT with 10 A-scans per line in patients with DME is comparable with the standard 100 scans per line. Measurement of ChT with a smaller number of frames would reduce patient discomfort and test time, and allow for larger areas to be imaged; thus, we used 10 ART frames in image capture as an average.
The results of this study of the subfoveal ChT in healthy controls were similar to those of Margolis and Spaide  (who used the same EDI-OCT technique), who reported a subfoveal ChT of 287 ± 76 μm in healthy individuals, and Copete et al. , who reported a subfoveal ChT of 286 ± 88 μm in healthy individuals using swept source OCT.
Our results were in agreement with those of Kim et al. , who found a significant increase in the subfoveal ChT as DR progressed in severity from moderate–severe NPDR to untreated PDR. The subfoveal choroid in the eyes of the DME group was significantly thicker than that in non-DME eyes.
Similar to our findings, Xu et al.  found that patients with DM had slightly, but statistically significant thicker subfoveal choroids. The presence and stage of DR, however, were not associated additionally with an abnormal subfoveal ChT. They suggested that DM, as a systemic disease, leads to a slight thickening of the choroid, but DR as an ocular disorder was not associated with Subfoveal ChT abnormalities after adjusting for the presence of DM.
Sarah et al.  suggested that there was an association between subfoveal ChT and the progression of DR rather than DME and that the choroid responds to the retinal vascular disease. They found that in PDR, there was a statistically significant increase in subfoveal ChT (242.1 μm) compared with the mild NPDR group (217.7 μm) (P = 0.03). DME was associated with a statistically nonsignificant increase in subfoveal ChT (225.4 μm) compared with eyes without DME (209.3 μm) (P = 0.13). This may reflect the higher incidence of more severe retinopathy in the eyes with DME, which is in agreement with our results.
The choroidal thickening mechanism in advanced DR is unknown. Savage et al. , using a computerized pneumotonometer, investigated pulsatile ocular blood flow as a reflection of choroidal circulation in eyes with DR. Compared with nondiabetic controls, choroidal blood flow was found to be increased in severe NPDR and PDR, but decreased in treated DR. These findings might reflect an increased production of vascular endothelial growth factor (VEGF) or other cytokines mediating choroidal vasodilation and elevation in choroidal blood flow, which subsequently increase the ChT, especially in patients with severe NPDR or PDR. The choroidal blood flow was found to be markedly decreased after laser pan retinal photocoagulation (PRP), possibly because of downregulation of VEGF; also, the choroid was found to be significantly thinner after PRP because of decreased blood flow and subsequent ischemic atrophic change .
Interestingly, different from our results, Esmaeelpour et al.  studied the ChT in diabetics using high-speed three-dimensional OCT imaging at 1060 nm. They observed choroidal thinning in diabetic compared with healthy eyes. Their study provided an overall idea about the effect of DM on ChT, but it used a different mean for choroidal image acquisition.
Different from this study, Querques et al.  noted that in diabetic eyes, there was an overall thinning of the choroid on EDI-OCT. A further reduction of ChT was detected in the presence of DME. These data favor the idea that, in diabetic eyes, decreased ChT may lead to tissue hypoxia and consequently an increase in the level of VEGF, resulting in the breakdown of the blood–retinal barrier and the development of macular edema. This contradiction can be explained by different patient profiles as their study included 63 eyes of diabetic patients with no healthy controls and the mean age was 65 ± 9 (48–83) years; elderly participants were included unlike our study, which may have induced bias as the choroids become thinner with age as noted by previous studies ,.
In contrast to our findings, Erkan et al. , using Optovue RTVue 100-2 (Optovue, Fremont, California, USA), studied 191 eyes: 151 eyes of DM patients (61 NPDR, 90 PDR) and 40 eyes of 20 healthy individuals; they found no statistically significant difference in ChT between normal individuals and the NPDR group. In the PDR group, there was a statistically significant decrease in ChT compared with both the healthy and the NPDR. They explained their results on the basis of previous histologic studies that reported atrophy and dropout of the choriocapillaris in eyes with DR . Histologic analysis is an invasive technique with shrinkage of tissue on fixation that is not directly comparable with our EDI-OCT study.
This contradiction can also be explained by different mean for image acquisition and different patient profiles as they studied unequal groups of 191 eyes, 151 eyes of DM patients and only 40 eyes of 20 healthy individuals, a limited number. Also, in their study, the patients in the PDR group were chosen from among only those with a history of PRP; these patients were excluded from our study. PRP was found to affect the central conduction time. Kim et al.  noted that PRP caused choroidal thinning and atrophy, explained, in part, by an intensive systemic control in this group as diabetic patients who had experienced any therapeutic measures, such as PRP, became more aware of the severity of the disease and were more likely to maintain strict blood sugar control evidenced by low HA1C levels in this group that is conceivable. Also, the reduction in VEGF following PRP played a significant role in reducing the ChT.
Regatieri et al. , using a Cirrus HD-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA), compared ChT in NPDR, PDR, and DME patients with healthy individuals and reported a significant decrease in ChT in the PDR and DME groups and a nonsignificant difference in the NPDR group. This contradiction may be because of different patient profiles as their study included unequal groups (49 eyes of diabetic patients and only 24 eyes of age-matched normal individuals) and the PDR group was chosen only from among those with a history of PRP; also, they used a different mean for image acquisition.
In this study, on correlating the age of healthy controls with ChT in different quadrants, a statistically significantly inverse correlation (decrease in ChCT with increase of age) was found. In contrast, in diabetics, a statistically significantly positive correlation (increase in ChT with increase of age) was found; this contradiction between both groups may be because of the reported positive effect of DM on ChT.
Margolis and Spaide  studied ChT in healthy individuals and noted that age had a statistically significantly inverse correlation with ChT. They observed that the subfoveal ChT decreased by 15.6 μm for each decade of life. Also, Spaide  reported that ChT decreased with age. With the randomized selection of the patients, we found that the mean age was 42 ± 7 years for diabetics and 39 ± 9 years for healthy controls, with no statistically significant difference (P = 0.16); thus, the age factor was eliminated.
Our findings were in agreement with those of Regatieri et al. , who studied ChT in 100 eyes divided into two equal groups on the basis of sex. They found no statistically significant difference in subfoveal ChT according to sex.
The limitations of this study were the low number of patients in the PDR group, n = 6 (12%), and that some patients had poor fixation leading to problems in the acquisition of good-quality scans, making the accurate measurement of ChT sometimes difficult. Some choroidal scans have a distinct hyporeflective line corresponding to the suprachoroidal space, but often, this line can be indistinct, leading to measurement variability or error. The placement of the calipers can also vary depending on the magnification of the scan on the screen.
| Conclusion|| |
ChT is closely correlated with the stage of DR. Progressive thickening of the choroid with the progression of DR and/or the development of DME may reflect the concurrent progression of diabetic choroidopathy.
EDI-OCT is a noninvasive technology that enables near-accurate assessment of choroidal vascular changes in diabetic patients.
This study was carried out in the Department of Ophthalmology, Menoufia University, and Embaba Ophthalmic Hospital.
This work was self-funded by the authors.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ciulla TA, Harris A, Latkany P. Ocular perfusion abnormalities in diabetes. Acta Ophthalmol Scand 2002; 80:468–477.
Nagaoka T, Kitaya N, Sugawara R. Alteration of choroidal circulation in the foveal region in patients with type 2 diabetes. Br J Ophthalmol 2004; 88:1060–1063.
Alm A. Ocular circulation. Hart WM, editor. Adler's physiology of the eye
ed. St. Louis, MO: CV Mosby; 1992. pp. 198–227.
McLeod DS, Lutty GA. High-resolution histologic analysis of the human choroidal vasculature. Invest Ophthalmol Vis Sci 1994; 35:3799–3811.
Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 2008; 146:496–500.
Ünsal E, Eltutar K, Zirtiloğlu S, Dinçer N, Ozdoğan Erkul S, Güngel H. Choroidal thickness in patients with diabetic retinopathy. Clin Ophthalmol 2014; 8:637–642.
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; 53:6017–6024.
Kim JT, Lee DH, Joe SG, Kim JG, Yoon YH. Changes in choroidal thickness in relation to the severity of retinopathy and macular edema in type 2 diabetic patients. Invest Ophthalmol Vis Sci 2013; 54:3378–3384.
Noori J, Riazi Esfahani M, Hajizadeh F, Zaferani M-M. Choroidal mapping; a novel approach for evaluating choroidal thickness and volume. J Ophthalmic Vis Res 2012; 7:180–185. [Full text]
Best W, Man R, Noonan JE, Xie J, Sandhu SS, Lamoureux EL, Centre for Eye Research Australia Choroidal thickness measurement with varying frame number in patients with diabetic macular edema. Invest Ophthalmol Vis Sci 2014; 55:1750.
Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol 2009; 147:811–815.
Copete S, Flores-Moreno I, Montero JA, Duker JS, Ruiz-Moreno JM. Direct comparison of spectral-domain and swept-source OCT in the measurement of choroidal thickness in normal eyes. Br J Ophthalmol 2014; 98:334–338.
Xu J, Xu L, Du KF, Shao L, Chen CX, Zhou JQ, et al.
Subfoveal choroidal thickness in diabetes and diabetic retinopathy. Ophthalmology 2013; 120:2023–2028.
Sarah Varughese R, Rewbury R, Want A, Chong V. Foveal choroidal thickness in patients with diabetic retinopathy and diabetic macular edema. Invest Ophthalmol Vis Sci 2014; 55:4431.
Savage HI, Hendrix JW, Peterson DC. Differences in pulsatile ocular blood flow among three classifications of diabetic retinopathy. Invest Ophthalmol Vis Sci 2004; 45:4504–4509.
Esmaeelpour M, Povazay B, Hermann B. Mapping choroidal and retinal thickness variation in type 2 diabetes using three-dimensional 1060-nm optical coherence tomography. Invest Ophthalmol Vis Sci 2011; 52:5311–5316.
Spaide RF. Age-related choroidal atrophy. Am J Ophthalmol 2009; 147:801–810.
Regatieri CV, Branchini L, Carmody J, Fujimoto JG, Duker JS. Choroidal thickness in patients with diabetic retinopathy analyzed by spectral-domain optical coherence tomography. Retina 2012; 32:563–568.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]