|Year : 2021 | Volume
| Issue : 1 | Page : 391-397
Comparison of choroidal thickness before and after injection of ranibizumab in patients with diabetic macular edema
Moatz F Elsawy1, Asmaa M Ibrahim1, Lamiaa T. M. Kashkoush2
1 Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Ophthalmology, Ophthalmology Hospital, Menoufia, Egypt
|Date of Submission||08-Aug-2020|
|Date of Decision||29-Sep-2020|
|Date of Acceptance||03-Oct-2020|
|Date of Web Publication||27-Mar-2021|
Lamiaa T. M. Kashkoush
Shebin El-Kom, Menoufia
Source of Support: None, Conflict of Interest: None
To compare choroidal thickness before and after injection of ranibizumab in patients with diabetic macular edema (DME) using enhanced depth optical coherence tomography (EDI-OCT).
DME is one of the most common complications of diabetic retinopathy (DR) and the most common cause of visual impairment. Intravitreal injection of antivascular endothelial growth factor is currently the most commonly used procedure for the treatment of DME.
Patients and methods
A prospective clinical study was conducted on 30 eyes of 27 patients of DME who underwent intravitreal injection of ranibizumab. A complete history was taken from all cases, and a full ophthalmologic examination was done. Fluorescein angiography and EDI-OCT were performed before injection and also at 1 month after injection. The difference between preoperative and postoperative subfoveal choroidal thickness was calculated.
The mean preoperative choroidal thickness measured subfoveally using EDI-OCT was 233.1 ± 20.22, whereas the mean of postoperative choroidal thickness after 1 month was 214.4 ± 19.61. The range of difference between preoperative and 1 month postoperative choroidal thickness using EDI-OCT was from 23 to 28 μm and the mean was 18.67 ± 8.99; the difference was calculated by subtracting the preoperative choroidal thickness from 1-month postoperative choroidal thickness.
There is a significant difference between the preoperative and 1-month postoperative choroidal thickness using EDI-OCT after injection of intravitreal ranibizumab in DME.
Keywords: antivascular endothelial growth factor, choroid, diabetic retinopathy, intravitreal injections, optical coherence tomography
|How to cite this article:|
Elsawy MF, Ibrahim AM, Kashkoush LT. Comparison of choroidal thickness before and after injection of ranibizumab in patients with diabetic macular edema. Menoufia Med J 2021;34:391-7
|How to cite this URL:|
Elsawy MF, Ibrahim AM, Kashkoush LT. Comparison of choroidal thickness before and after injection of ranibizumab in patients with diabetic macular edema. Menoufia Med J [serial online] 2021 [cited 2021 May 8];34:391-7. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/391/312041
| Introduction|| |
Diabetic retinopathy (DR) is the leading cause of blindness in persons aged 25–74 years in the United States. The exact mechanism by which diabetes causes retinopathy remains unclear, but several theories have been postulated to explain the typical course and history of the disease ,.
DR is the result of microvascular retinal changes. Hyperglycemia-induced intramural pericytes death and thickening of the basement membrane lead to incompetence of the vascular walls .
Diabetic macular edema (DME) is the swelling of the retina resulting from the exudation and accumulation of extracellular fluid and proteins in the macula .
Exudation arises from structural changes in the endothelium of retinal vasculature, which lead to the breakdown of the blood–retina barrier and increase in vascular permeability .
Nearly half of the world's diabetic population has some degree of DR, and DME is a leading cause of blindness in these patients. The prevalence is dramatically increased in eyes with more severe retinopathy ,.
In DME, the development of retinal ischemia leads to an increase in production of vascular endothelial growth factor (VEGF-A), which increases vascular permeability by affecting endothelial tight junction proteins .
Histopathologic studies also have implicated choroidal dysfunction in diabetics. These changes include loss of the choriocapillaris, increased tortuosity, narrowing and dilation of vessels, and sinus-like structure formation between choroidal lobules .
The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF each administered by intraocular injection have been tested in prospective randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation and avoids the ocular adverse effects associated with laser treatment; thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients .
Currently, there are two main anti-VEGF therapies for the treatment of ocular disorders, each of which targets a distinct set of VEGF-a isoforms .
All isoforms carry the plasmin cleavage site and have the potential to be cleaved by plasmin to generate a smaller form .
Ranibizumab is a fully humanized monoclonal anti-VEGF-A fab fragment developed specifically for ophthalmic applications. Ranibizumab was designed to blind all biologically active forms of VEGF-A .
Ranibizumab previously FDA approved for intravitreal injection in patients with age-related macular degeneration gained FDA approval to treat DME in August 2012 .
As ranibizumab exerts an anti-VEGF-A effect on the retinal blood vessels, it also does the same for choroidal vasculature. The anti-VEGF effect in the choroidal circulation is similar to retina in many ways, but it has not been fully studied, as there are only few clinical studies on choroidal changes in diabetes because of the difficulty of imaging the choroid in vivo .
Choroid is a highly vascularized tissue, which can be a place for development of diabetic vasculopathy. Histologic evaluation of choroid in diabetic patients has demonstrated increased rate of arteriosclerosis and deposition of periodic acid-Schiff-positive material in the thickened wall of choroidal vessels. In addition, occluded choroidal vessels, capillary dropout, vascular remodeling, microaneurysms, and choroidal neovascularization have been reported histologically .
A new imaging technique depending on spectral domain optical coherence tomography (SD-OCT) was introduced by Spaide et al. . This technique enables better visualization of choroid. EDI-OCT is a simple modification of the conventional SD-OCT technique, made possible by image inversion to apply more light exposure to outer parts of the choroid. This technique involves a slight displacement of the image capturing machine, computerized image averaging, high-speed scanning, AND eye-tracking system.
A better clinical understanding of choroidal damage might be important for an accurate assessment of diabetic eye disease, but adequate visualization of the choroid using OCT has not been possible until recently, owing to its posterior location and the presence of pigmented cells that attenuate the incident light. Recent reports showed successful examination and measurement of choroidal thickness in normal and pathologic states using the Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) .
Enhanced depth imaging (EDI) using SD-OCT enables improved visualization of the choroid and assessment of choroidal thickness. Results of clinical studies have indicated that choroidal thickness may be related to DR severity, and the presence of DME is associated with a significant decrease in choroidal thickness .
The aim of this study was to compare choroidal thickness before and after injection of ranibizumab in patients with DME using EDI-OCT.
| Patients and methods|| |
A prospective interventional clinical study was conducted on 30 eyes of 27 patients from Ophthalmology Outpatient Clinic at Menoufia University Hospital between January 2019 to January 2020 with DME after approval of the medical ethics committee and signing a written informed consent.
This study was conducted on patients with DR of both sexes aged from 42 to 71 years with diabetic macular edema, with baseline central macular thickness of 400 μm or more diagnosed by OCT.
Previous retinal laser therapy, patients with repaired retinal detachment, patients with atrophic macular scars, patients with age-related macular degeneration, patients with high myopia, patients with posterior staphyloma, patients with previous pars plana vitrectomy, patients with ischemic maculopathy, and patients with tractional DME were excluded.
A prospective clinical study was conducted on 30 eyes of 27 patients of DME who underwent intravitreal injection of ranibizumab (Lucentis; Novartis, Basel, Switzerland). Informed consent was obtained from all patients after explanation of the nature of the present study, and all patients were subjected to the following.
Detailed history taking including, age, sex, medical, history, and the duration of diabetes was done. Surgical history such as cataract surgery, recent vitrectomy, previous retinal laser treatment, or retinal detachment repair was also taken.
Full ophthalmological examination was done: best-corrected visual acuity (BCVA) was measured using Snellen chart at 6 m, and the values were converted to decimal for statistical analysis. Refraction was done by Topcon autorefractometer KR900 (Topcon Inc., Tokyo, Japan) to exclude high myopia. Slit lamp examination was done for every patient, with examination of the iris for neovascularization. Examination of the lens for the presence of cataract or pseudophakia was done. Detailed fundus examination with slit lamp and volk 90 was done. Confirmation of the presence of DME was done. The presence of retinal neovascularization was assessed to identify patients with proliferative DR and patients with nonproliferative DR. Exclusion of the presence of laser retinal scars, the presence of repaired retinal detachment, the presence of atrophic macular scars, and the presence of posterior staphyloma was done as well.
FA was done using Topcon TRC-50; Topcon Corporation, Japan. The patient was informed about the steps of the procedure and the pupil was dilated. Baseline color and red-free filtered (black and white) images are taken before injection. A bolus injection of 2–5 ml of sodium fluorescein into a vein in the arm or hand was done; the normal adult dose is 500 mg. A series of black and white digital photographs are taken of the retina before and after the fluorescein reaches the retinal circulation. Patients with ischemic maculopathy were excluded.
OCT was done using spectral domain, Heidelberg-OCT, using EDI technique. The patient was informed about the steps of the procedure, and the pupil was dilated. OCT image was acquired, and then the subfoveal choroidal thickness (within 100 M from the fovea) was measured manually using the manual measuring ruler from the outer edge of the hyperreflective retinal pigment epithelium to the inner sclera.
Data were collected, tabulated, and statistically analyzed using a personal computer with statistical package of social science (SPSS), version 20.0 (IPM Corp., Armonk, New York, USA) where the following statistics were applied.
Data were statistically described in terms of mean, SD, median, and range, or frequencies and percentages when appropriate. Preoperative and postoperative choroidal thicknesses were compared using paired t test, and Wilcoxon signed-rank test (Z) was used for comparing between preoperative and postoperative BCVA. SD is presented if relevant. P values less than 0.05 were considered statistically significant.
| Results|| |
The study was conducted on 30 eyes of 27 patients with DME undergoing intravitreal injection of Lucentis and measuring the choroidal thickness before and after the injection by EDI-OCT. The data were collected, tabulated, and analyzed as follows: regarding demographic data of the patients, with respect to (a) sex, the studied cases included 13 males, with a percentage of 43.3%, and 17 females, with a percentage of 56.7%, and (b) age, the range of age in studied cases age was from 42 and 71 years, and the mean of age was 59.40 ± 8.45 years [Table 1] and [Figure 1].
|Table 1: Distribution of the studied cases according to demographic data and according to diabetic macular duration and diabetic macular severity (n=30)|
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Regarding preoperative and postoperative BCVA, the mean preoperative BCVA (decimal scale) was 0.21 ± 0.10, with a range from 0.1 to 0.40, and the mean postoperative BCVA (decimal scale) was 0.31 ± 0.12, with a range from 0.10 to 0.50 [Table 2] and [Figure 2].
|Table 2: Comparison between preoperative and postoperative according to best-corrected visual acuity|
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|Figure 2: Comparison between preoperative and postoperative according to BCVA. BCVA, best-corrected visual acuity.|
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Regarding preoperative and 1-month postoperative choroidal thickness, the mean preoperative choroidal thickness measured subfoveally using EDI-OCT was 233.1 ± 20.22 μm, with a range of 195 to 268 μm, whereas the mean postoperative choroidal thickness after 1 month was 214.4 ± 19.61 μm, with a range of 172–240 μm [Table 3] and [Figure 3].
|Table 3: Comparison between preoperative and 1 month postoperative choroidal thickness using enhanced depth optical coherence tomography|
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|Figure 3: Comparison between preoperative and 1-month postoperative choroidal thickness.|
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The range of difference between preoperative and 1 month postoperative choroidal thickness using EDI-OCT was from 23 to 28 μm, and the mean was 18.67 ± 8.99 μm. The difference was calculated by subtracting the preoperative choroidal thickness from 1-month postoperative choroidal thickness [Table 4].
|Table 4: Difference between preoperative and 1 month postoperative choroidal thickness using enhanced depth optical coherence tomography|
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The result showed a significant difference between the preoperative and 1-month postoperative choroidal thickness using EDI-OCT after injection of intravitreal Lucentis in DME, as P value was less than 0.001.
| Discussion|| |
More than 90 million people worldwide are affected by DR, causing significant vision loss , with macular edema and proliferative retinopathy as the leading causes of visual impairment .
Anti-VEGF drugs are widely used in the treatment of DME; this is supported by an extensive body of literature, demonstrating substantial improvements in visual and anatomic outcomes ,.
The choroid is a vascularized tissue that plays a vital role in providing metabolic support to the outer retina, including the photoreceptors and prelaminar portion of the optic nerve head .
EDI using SD-OCT enables improved visualization of the choroid and assessment of choroidal thickness ,. Results of clinical studies have indicated that choroidal thickness may be related to DR severity, and the presence of DME is associated with a significant decrease in choroidal thickness .
Currently, intravitreal anti-VEGF injections are the most common treatment for DME. Although anti-VEGF injections improved visual acuity, several studies demonstrated an association with decreased central retinal thickness . However, there is currently a lack of studies investigating the effect of anti-VEGF injections on the choroid in patients with diabetes.
Many researchers have been concerned about studying the choroidal changes in diabetic eye diseases using choroidal thickness as a reference; however, the effect of anti-VEGF injection as treatment for DME on the choroidal circulation is another issue that needs to be studied carefully. Our study aimed at studying the effect of Lucentis on choroidal thickness ,.
Our study was performed on 30 eyes of 27 patients who had intravitreal injection of Lucentis. The age range was from 42 and 71 years, with a mean of 59.40 ± 8.45 years. A total of 17 (56.7%) eyes were of females and the other 13 (43.3%) eyes were of males. Anterior and posterior segment examination before and after injection was done to all cases and also their BCVA was measured before and after injection. Fluorescein angiography was done preoperatively, whereas EDI-OCT with choroidal thickness measurement was done preoperatively and 1 month postoperatively to compare the results. Follow-up period is short, and this is a limitation of our study.
In our study, we used the EDI technique to evaluate the choroidal thickness. We stressed on the central subfoveal choroidal thickness to eliminate the anatomical variation, and we measured the choroid using the same guidelines from previous studies, which is perpendicularly from the outer edge of the hyperreflective retinal pigment epithelium to the inner sclera . We found significant changes between the preoperative and the postoperative measures, and the results are as follows: the mean of preoperative choroidal thickness measured subfoveal using EDI-OCT was 233.1 ± 20.22 with a range from 195 to 268 μm.
Ozdogan Erkul et al. evaluated subfoveal choroidal thickness of normal eyes with the use of the EDI technique of OCT and founded that the mean subfoveal choroidal thickness was 280.23 lm (SD ± 81.15, range 124–527 lm).
However, Nourinia et al. assessed choroidal thickness and central macular thickness in patients with DR, and choroidal thickness was found to be significantly decreased in the DME and proliferative DR groups.
In our study at the postoperative period of 1 month, the mean preoperative choroidal thickness measured subfoveal using EDI-OCT was 233.1 ± 20.22 μm, with a range from 195 to 268 μm, whereas the mean postoperative choroidal thickness after 1 month was 214.4 ± 19.61 μm, with a range of 172–240 μm. The postoperative choroidal thickness was found to be significant (P < 0.001) lower than the preoperative choroidal thickness by a mean difference of 18.67 ± 8.99.
Similar to our study, Kniggendorf et al. evaluated choroidal thickness at baseline and after intravitreal anti-VEGF treatment in patients with DME and found that mean nasal, subfoveal, and temporal choroidal thickness measurements at baseline were 234.10 ± 8.63, 246.89 ± 8.94, and 238.12 ± 8.20 μm, respectively, and those at 6 months after treatment were 210.46 ± 8.00, 215.66 ± 8.29, and 212.43 ± 8.14 μm, respectively. Significant differences in CT were observed between baseline and the follow-up at all measured points (P = 0.0327)
From the studies done in post-anti-VEGF injection in diabetic patients, Rayess et al. reported that after 3 monthly anti-VEGF treatments, subfoveal choroidal thickness decreased significantly (225 mm at baseline and 201 mm at 3 months, P < 0.0001).
Yiu et al. also found that choroidal thickness decreased significantly at the fovea (246.6–224.8 mm; P < 0.001) in 59 eyes with DME, where eyes were treated with anti-VEGF injections.
Our finding also is in agreement with Yiu et al. , who demonstrated that central choroidal thickness decreased significantly at the fovea (246.6–224.8 μm; P < 0.001) following anti-VEGF therapy.
In the present study, we measured the mean preoperative BCVA, which was 0.21 ± 0.1, in range from 0.1 and 0.4, on Snellen's chart in the studied cases, whereas the mean postoperative BCVA was 0.31 ± 0.12, in range from 0.3 and 0.5; this was statistically significant (P ≤ 0.001) to confirm the positive effect of Lucentis injection on BCVA.
Our study was supported by other studies done on the effect of Lucentis injection on BCVA, as Yiu et al. found in their study on 59 eyes from 59 patients with DME that eyes treated with anti-VEGF injections showed an improvement in mean BCVA from 0.501 to 0.424 (P = 0.026).
The findings of our study compared favorably also with Park et al. , who reported that the mean preoperative BCVA on Snellen's chart was 0.6 ± 0.3, whereas the mean postoperative BVCA on Snellen's chart was 0.7 ± 0.3, implying a good visual outcome after intravitreal injection of Lucentis.
We also studied the relation between the postoperative choroidal thickness and postoperative BCVA, which was negative (r=−0.253) and was statistically insignificant (P = 0.177), which is in agreement with Yiu et al. , who reported a negative relation between central choroidal thickness and BCVA (R2 = 0.017; P = 0.470) after injection of anti-VEGF therapy for DME and the decrease of central choroidal thickness may not be associated with functional or anatomical outcomes in eyes with DME.
| Conclusion|| |
Intravitreal injection of Lucentis is an effective treatment for DME, which has a direct effect on both the retina and the choroid.
EDI using SD-OCT enables improved visualization of the choroid in vivo and assessment of choroidal thickness. There was a significant difference between the preoperative subfoveal choroidal thickness and 1-month postoperative subfoveal choroidal thickness after injection of ranibizumab.
Reduction in choroidal thickness after intravitreal injection of ranibizumab can be an indicator for its effectiveness [Table 5].
|Table 5: Relation between choroidal thickness, age, sex, diabetic macular severity, and diabetic macular duration|
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]