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 Table of Contents    
Year : 2021  |  Volume : 14  |  Issue : 3  |  Page : 179-183  

Intravitreal Ozurdex has no short term influence on choroidal thickness and vascularity index in eyes with diabetic macular edema: A pilot study

1 Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, 2Elite School of Optometry, Medical Research Foundation, Sankara Nethralaya, Chennai, Tamil Nadu, India
2 Elite School of Optometry, Medical Research Foundation, Sankara Nethralaya; Srimati Sundari Subramanian Department of Visual Psychophysics, Sankara Nethralya, Chennai, Tamil Nadu, India
3 National Healthcare Group Eye Institute, Tan Tock Seng Hospital; School of Material Science and Engineering, Nanyang Technological University, Singapore

Date of Submission05-Jan-2021
Date of Decision08-May-2021
Date of Acceptance21-Jun-2021
Date of Web Publication20-Oct-2021

Correspondence Address:
Dr. Pukhraj Rishi
Shri Bhagwan Mahavir Vitreoretinal Services, Sankara Nethralya, 18 College Road, Chennai - 600 006, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ojo.ojo_7_21

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AIM: To analyze choroidal parameters in eyes with diabetic macular edema (DME) treated with intravitreal Ozurdex.
PATIENTS AND METHODS: Twenty eyes of 14 patients were included in this prospective study. Optical coherence tomography images were obtained before and 8–10 weeks after intravitreal Ozurdex injection; binarized and subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) were calculated.
RESULTS: Mean SFCT (treatment naïve; 242.22 ± 32.87 reduced to 218.10 ± 22.10, P = 0.158 and previously treated; 330.4 ± 56.72 reduced to 328.93 ± 50.55, P = 0.833) and mean CVI (treatment naïve; 0.64 ± 0.03 changed to 0.65 ± 0.04, P = 0.583 and previously treated; 0.65 ± 0.05 reduced to 0.64 ± 0.03, P = 0.208) showed no significant change.
CONCLUSION: Intravitreal Ozurdex showed no significant effects on SFCT and CVI in eyes with DME over short term. Larger studies with longer follow-up may allow a better understanding.

Keywords: Choroid, choroidal thickness, choroidal vascularity index, eye, intravitreal injection, optical coherence tomography, Ozurdex

How to cite this article:
Rishi P, Verma A, Akhtar Z, Agrawal R, Agrawal A, Kalluri Bharat RP, Rishi E. Intravitreal Ozurdex has no short term influence on choroidal thickness and vascularity index in eyes with diabetic macular edema: A pilot study. Oman J Ophthalmol 2021;14:179-83

How to cite this URL:
Rishi P, Verma A, Akhtar Z, Agrawal R, Agrawal A, Kalluri Bharat RP, Rishi E. Intravitreal Ozurdex has no short term influence on choroidal thickness and vascularity index in eyes with diabetic macular edema: A pilot study. Oman J Ophthalmol [serial online] 2021 [cited 2023 Feb 2];14:179-83. Available from: https://www.ojoonline.org/text.asp?2021/14/3/179/328613

   Introduction Top

Since the introduction of enhanced depth imaging optical coherence tomography (OCT) in clinical practice and research studies, significant advances have been made in understanding the association of choroidal changes in various retinochoroidal diseases.[1],[2] So far, various studies have relied on the choroidal thickness (CT) to document the changes taking place in choroid in various diseases and in response to therapy.[3],[4],[5] The most reliable measurement of the CT is in the subfoveal region, and it definitely overlooks the other vascular changes that might undergo variations as a part of a disease process.[6] The choroidal vascularity index (CVI), i.e., the proportion of the luminal area to the total choroidal area, has recently been proposed to be an excellent quantitative indicator of the vascular status of the choroid in health and disease.[2],[7] This takes precedence considering the fact that histological studies of choroid are unable to yield accurate information about the vascular status of the tissue.[8]

Changes in choroid have been shown to play a pivotal role in pathogenesis of diabetic retinopathy (DR).[9],[10],[11],[12] More importantly, researchers have tried to establish a correlation between choroidal changes and treatment with steroids in eyes with DME.[13] CT is the only parameter that has been investigated in this regard. While some researchers have failed to reach a consensus about the CT in DME,[9],[14],[15] others like Sonoda et al.[13] showed a reduction in CT after treatment with steroids. Apart from changes in CT, the effects of steroids on the choroid in these eyes are still less well understood. As the etiology of DME is multifactorial, the effect of various treatment modalities may vary.[16] Nonetheless, there is a paucity in literature regarding the effects of steroids on CT and CVI in these eyes. We analyzed CT and CVI in such eyes treated with sustained release dexamethasone implant over short term.[17],[18],[19]

   Patients and Methods Top

This was a prospective, observational study approved by the Institutional Review Board of Medical Research Foundation, Chennai, India. The study adhered to the tenets of the Declaration of Helsinki. Patients were enrolled between July 2015 and September 2016. Informed consent was obtained from all the patients prior to enrollment. All participants underwent a detailed ocular examination including best-corrected visual acuity using Snellen's chart, slit-lamp biomicroscopy, and dilated fundus evaluation by indirect ophthalmoscopy. The glycemic status, including glycosylated hemoglobin HbA1c if available, was noted.

Inclusion criteria

  1. Eyes of subjects with diabetes mellitus having DME
  2. Age >18 years
  3. Consenting for participation in the study.

Exclusion criteria

  1. Prior history of retinal laser/antivascular endothelial growth factor (VEGF) injection/intraocular steroid injection in the last 3 months
  2. History of glaucoma
  3. Prior surgery like cataract/vitreoretinal surgery
  4. High myopia >‒6 Diopters.
  5. Other coexistent retinal diseases.

Intravitreal injection procedure

Written informed consent was obtained prior to injection procedure from all the patients. Pupillary dilatation was carried out with tropicamide eye drops (1%), instilled twice with a gap of 5 min. Proparacaine hydrochloride 1% ophthalmic solution (Paracaine) eye drops were instilled in the conjunctival cul-de-sac 3 times at an interval of 5 min for adequate anesthesia. Povidone iodine eye drops (5%) were instilled twice with a gap of 1 min prior to the injection. The eye was routinely cleaned with povidone iodine skin preparation (10%) and a sterile drape was placed. The dexamethasone implant was injected into the pars plana region, 3.5 mm away in the inferotemporal quadrant by the surgeon, and the same was confirmed with indirect ophthalmoscope fundus examination immediately after the injection. The eye was patched with a sterile eye patch.

Image acquisition

Scans were acquired using Swept source OCT (SSOCT, DRI-OCT-1 Atlantis; Topcon, Tokyo, Japan); 12-mm horizontal, vertical, and radial scans centered on the fovea as described in the section of “CT measurement,” were obtained.

Central foveal thickness

The CFT was measured manually using the calipers, by drawing a straight line from the foveal center from the outer edge of internal limiting membrane (ILM) till the inner edge of retinal pigment epithelium (RPE). Foveal center was defined in a B scan passing through the fovea with a hyper-reflective dot echo at the level of ILM.

Choroidal thickness

OCT scans were obtained using SS-OCT (Deep Range Imaging, OCT-1, Atlantis, Topcon, Tokyo, Japan).[20] Scan used for imaging is a 12-mm horizontal, vertical, and radial scan (×2) centered on fovea. Measurements were taken at fovea and at 500 microns interval nasal, temporal, superior, inferior, inferonasal, superotemporal, inferotemporal, and superonasal up to 3000 microns from the fovea [Figure 1]. CT was measured from the base of hyperreflective RPE-Bruch's membrane to the choroid–scleral interface. Six measurements were taken for each quadrant and average values were used for analysis. For each eye, CT was measured at 52 different points. A mean CT for each quadrant (temporal, nasal, superior, inferior, superonasal, inferotemporal, superotemporal, and inferonasal) was obtained by calculating the average value of 6 points for each quadrant. All measurements were manually recorded. Variability in the manual measurement was assessed for 15 random eyes using a horizontal line scan. Measurements were repeated by two masked observers for 13 different locations including subfoveal and 6 different locations nasal and temporal to fovea. Interobserver variability was assessed by comparing the values between two observers. Repeatability of the manual measurements was assessed by repeating the measurements twice at 13 different locations by the same observer using the horizontal line scan with minimum time gap of 1 week. All examination procedures were conducted between 11:00 am and 3:00 pm to control for diurnal variation. The CFT and CT measurements were performed by 2 independent certified graders to assess the intragrader agreement (intraclass correlation coefficient, ICC).
Figure 1: At presentation, SS-optical coherence tomography image of right eye with diabetic macular edema (a) and binarized image of the same optical coherence tomography (b). Six weeks after intravitreal Ozurdex injection, optical coherence tomography reveals significant reduction of diabetic macular edema (c) and binarized image of the postinjection optical coherence tomography (d)

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Choroidal vascularity index

CVI was calculated using the same raster scan after binarization, as described by Agrawal et al.[2] Images were binarized and CVI was calculated using ImageJ software version 1.50 (National Institute of Health, Bethesda, MD 20892, USA) [Figure 1]. The choroid–scleral interface was delineated with binarization using Niblack's autolocal threshold tool. A subfoveal area of 1.5 mm width, delineated by upper border of RPE and lower border of CSI [Figure 2] was used to calculate the total circumscribed choroidal area (TCA), luminal (dark pixels) area (LA), and the stromal (white pixels) area (SA). CVI was calculated as the proportion of LA to the TCA and was expressed in percentage.
Figure 2: A subfoveal area of 1.5 mm width (yellow), delineated by upper border at rated perceived exertion and lower border at the choroid-scleral interface, is used to calculate the total circumscribed choroidal area, luminal (dark pixels) area, and the stromal (white pixels) area. Choroidal vascularity index is calculated as the proportion of luminal (dark pixels) area to the total circumscribed choroidal area, expressed in percentage

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Statistical analysis

Descriptive analysis was employed to compare between treatment naïve and previously treated eyes. The Fisher's exact test or Chi-square test was used to compare frequencies of categorical variables as appropriate. CT and CFT were measured at baseline and at 8–10 weeks after Ozurdex injection and the changes were evaluated using Wilcoxon Signed–Rank test and Mann–Whitney U-test. All the analyses were performed using SPSS version 20.0 (IBM Corp., Armonk, New York, USA) and the statistical significance was tested at 5%.

   Results Top

Twenty eyes of 14 subjects were recruited in this study. Eleven subjects were male.

The mean age at presentation was 60 ± 5 (range, 52–69) years. All subjects had Type II diabetes, with a mean duration being 14.95 ± 5.8 (range, 2–22) years. Of 20 eyes, 6 eyes (30%) were treatment naïve eyes; 6 eyes (30%) received prior anti-VEGF injections (mean number 1.15 [standard deviation (SD) = ±1.3; range: 0–3]/eye); 3 eyes (15%) received prior Ozurdex injections (mean number 1.35 [SD = ±2.4; range: 0–10]/eye); and 5 eyes (25%) received a combination of both anti-VEGF and Ozurdex injections prior to enrolment into the study. The mean values of clinical parameters before and after intravitreal Ozurdex injection in the study cohort are given in [Table 1]. When compared between treatment naïve and previously treated (Ozurdex, anti-VEGF, and combined injections) eyes [Table 2], there was no statistically significant difference before and after the injection Ozurdex.
Table 1: Comparison of parameters before and after injection in the study cohort

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Table 2: Comparison of parameters before and after injection in treatment naïve versus eyes previously treated with Oxurdex™, antivascular endothelial growth factor and combined injections

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However, when the previously treated eyes were grouped together, CMT showed significant reduction following Ozurdex injection in treatment naïve (478.3 ± 257.82-358.87 ± 196.18; P = 0.003) as well as previously treated (597.17 ± 171.38-393.96 ± 171.03; P = 0.05) groups. The corresponding subfoveal CT (treatment naïve; 242.22 ± 32.87-218.10 ± 22.10, P = 0.158 and previously treated; 330.4 ± 56.72-328.93 ± 50.55, P = 0.833) and CVI (treatment naïve; 0.64 ± 0.03-0.65 ± 0.04, P = 0.583 and previously treated; 0.65 ± 0.05-0.64 ± 0.03, P = 0.208) showed no significant change.

   Discussion Top

The results of this study clearly indicate that the dexamethasone implant had no significant short-term effects on either the thickness or the vascularity index in choroid in eyes with DME. This was true even when the treatment naïve eyes were compared with previously treated eyes grouped together, or analyzed individually (following Ozurdex, anti-VEGF, or both). As inflammation has been shown to play a major role in the pathogenesis of DME, the role of steroids in reducing the macular edema and therefore macular thickness has been well known.[21],[22],[23] A few studies have also demonstrated the presence of inflammatory cells in the choroid and dropout of microvessels from the choroid in eyes with DME.[24],[25]

A spontaneous decrease in CT in eyes with neovascular age-related macular degeneration is well known.[26] A prospective study on Indian patients has also shown reduction in CT in diabetic patients, with or without DR, as compared to healthy subjects.[27] Recent investigators have also shown decreased CT in DME and Proliferative DR.[9],[28] Moreover, a few studies reported a reduction in CT in DME after anti-VEGF therapy[29] and intravitreal triamcinolone injection.[13] However, adequate evidence supporting the changes in choroid after intravitreal dexamethasone injection in such eyes is lacking. While some researchers have failed to reach a consensus about the CT in DME,[9],[14],[15] others like Sonoda et al. showed a reduction in CT after treatment with steroids.[13] As the etiology of DME is multifactorial, the effect of various treatment modalities would vary.[16]

The increased expression of inflammatory mediators like intracellular adhesion molecule-1 as well as E- and P-selectins throughout the choroidal vasculature in diabetic eyes shows involvement of choroidal tissue in pathogenesis of DME.[24] Nonetheless, without adequate evidence, clinical involvement of choroidal tissue in response to intravitreal dexamethasone is less well understood. Ours is the first study, which points out the short-term changes taking place in choroid in response to intravitreal Ozurdex™ in such eyes. Since Ozurdex does not appear to influence the subfoveal CT or choroidal vascularity indices in eyes with DME over the short-term, it is unlikely to act as a disease modifying agent in such eyes. The long-term effects of intravitreal dexamethasone injection on choroidal tissue will require a larger longitudinal study.

This study has some limitations. First, the sample size is small. Second, it is a cross-sectional analysis. Larger, prospective trials with adequate numbers in each group and a longer follow-up may highlight choroidal changes in response to intravitreal Ozurdex.

Summary statement

This study analyzes choroidal structures in 20 eyes of 14 subjects with diabetic macular edema (DME) using image binarization on swept source optical coherence tomography. There were no significant differences in subfoveal choroidal thickness or choroidal vascularity indices before and after Ozurdex injection in treatment naïve as well as previously treated eyes over a short-term period.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

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[PUBMED]  [Full text]  
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  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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