Choroidal thickness prognostic indicator for visual improvement in central retinal vein occlusion

Hoda M. K. EI-Sobky; Marwa A Zaky; Mohamed F Elhamadan

doi:10.4103/mmj.mmj_28_20

ORIGINAL ARTICLE

Year : 2020 | Volume : 33 | Issue : 4 | Page : 1139-1143

Choroidal thickness prognostic indicator for visual improvement in central retinal vein occlusion

Hoda M. K. EI-Sobky¹, Marwa A Zaky¹, Mohamed F Elhamadan²
¹ Department of Ophthalmology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
² Department of Ophthalmology, Menouf Ophthalmology Hospital, Menoufia, Egypt

Date of Submission	02-Feb-2020
Date of Decision	22-Mar-2020
Date of Acceptance	28-Mar-2020
Date of Web Publication	24-Dec-2020

Correspondence Address:
Mohamed F Elhamadan
Menoufia
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/mmj.mmj_28_20

Abstract

Objective
The aim was to study the relationship between baseline choroidal thickness and functional improvement in central retinal vein occlusion (CRVO) patients receiving antivascular endothelial growth factor (VEGF) therapy.
Background
CRVO is one of the most common vascular diseases of the retina that seriously affect visual acuity.
Design
Prospective study.
Patients and methods
Forty eyes of 40 patients with CRVO were included. All patients received anti-VEGF treatment (Ranibizumab) three injections 1 month apart. Enhanced depth imaging optical coherence tomography was used to evaluate choroidal thickness and macular thickness at baseline and after treatment. Also, best-corrected visual acuity was documented before and after treatment as a sign of functional improvement.
Results
Forty eyes of 40 patients with CRVO were included. Patients were classified into two groups according to their improvement in visual acuity: the responder group in whom visual acuity gain greater than or equal to two lines and the nonresponder group in whom visual acuity gain less than two lines. Baseline choroidal thickness in CRVO eyes (259 ± 37.9 μm) was thicker than in their fellow eye (202.5 ± 21.8 μm) (P = 0.001). Mean choroidal thickness at baseline for functional responders (259.2 ± 37.9 μm) was greater than that of nonresponders (224.9 ± 33.6 μm) (P = 0.005). On multivariate analysis a thicker baseline choroidal thickness (<237 μm) was found to be a positive indicator for visual improvement (odds ratio = 2.45; P = 0.025), Also, age (<60 years old) was a positive indicator for visual improvement (odds ratio = 2.39; P = 0.036).
Conclusion
Initial choroidal thickness and the age of patients can be used as a prognostic indicator for functional improvement in CRVO patients receiving anti-VEGF treatment.

Keywords: antivascular endothelial growth factor, central retinal vein occlusion, choroidal thickness, enhanced depth imaging optical coherence tomography, intravitreal injection

How to cite this article:
EI-Sobky HM, Zaky MA, Elhamadan MF. Choroidal thickness prognostic indicator for visual improvement in central retinal vein occlusion. Menoufia Med J 2020;33:1139-43

How to cite this URL:
EI-Sobky HM, Zaky MA, Elhamadan MF. Choroidal thickness prognostic indicator for visual improvement in central retinal vein occlusion. Menoufia Med J [serial online] 2020 [cited 2021 Apr 18];33:1139-43. Available from: http://www.mmj.eg.net/text.asp?2020/33/4/1139/304502

Introduction

Central retinal vein occlusion (CRVO) is one of the most common vascular disorders of the retina. Most of the patients are above 55 years of age. CRVO can occur in young patients due to coagulation defects. CRVO occurs in one eye usually, but these patients are susceptible to other vascular diseases in the other normal eye, but affection of both eyes is very rare^[1].

Antivascular endothelial growth factor (VEGF) therapy has become the drug of choice in CRVO as it enhances retinal perfusion, lowers intravenous pressure, and normalizes venous diameter and tortuosity^[2].

Enhanced depth imaging optical coherence tomography (EDI-OCT) can show choroidal structure and evaluate many chorioretinal abnormalities^[3].

Many studies have evaluated choroidal thickness in retinal vein occlusion eyes and compared it with choroidal thickness in their other normal eyes. Some of these studies have found that choroidal thickness is significantly thicker in diseased eyes than their corresponding fellow eye^[4],[5],[6]. However, another study had found that there is no significant difference in choroidal thickness between diseased eyes and their corresponding fellow eyes^[7].

There are choroidal thickness changes in newly diagnosed CRVO patients with secondary macular edema as intraocular VEGF level increases due to retinal ischemia which increases choroidal vessel permeability and thickness^[8].

In our study, we investigated changes in choroidal thickness in CRVO patients initially and after anti-VEGF therapy, and compared between choroidal thickness in CRVO eyes and their corresponding fellow eyes. In addition to that we evaluated the relationship between initial choroidal thickness and visual acuity improvement (functional improvement) in CRVO patients.

Patients and Methods

The present study evaluated 40 CRVO patients from the outpatient clinic of Menoufia University Hospital from August 2017 to February 2018. Approval of the Medical Ethics Committee of Menoufia University (certificate number 121-1-9-2017) and written consent from all patients were obtained. All patients included were treated with three successive anti-VEGF injections 1 month apart. Anti-VEGF (Ranibizumab) used was from Lucentis (Novartis Pharma Stein AG, Stein, Switzerland). Follow-up of the patients were done clinically and multiple EDI-OCT scans using Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) evaluated choroidal thickness and macular thickness at baseline and after treatment.

The inclusion criteria for this study were recently diagnosed CRVO with secondary macular edema (central macular thickness <300 μm) receiving anti-VEGF therapy. While the exclusion criteria were any patient who had eye surgery rather than cataract surgery, any other ocular disease as diabetic macular edema, choroidal neovascularization, age-related macular degeneration, or patients who received other treatments for CRVO such as subtenon or intravitreal corticosteroid or laser photocoagulation.

Patients were classified into two groups according to their improvement in visual acuity: the responder group in whom visual acuity gain greater than or equal to two lines and the nonresponder group in whom visual acuity gain less than two lines.

All patient data were collected such as age, sex, past medical history (hypertension, diabetes mellitus), best-corrected decimal chart visual acuity (BCVA) based on spectacle correction, intraocular pressure using Goldmann applanation tonometer, anterior segment examination for the cornea and iris (for iris neovascularization) were done using slit lamp. Fundus examination for the retina, optic nerve head, and vitreous body were done by slit lamp and auxiliary lens (vol k+90 D) after pupillary dilatation. Anti-VEGF (Ranibizumab) injection:

Surgical procedure: all injections were done with the same technique (by Dr Mrawa Aly Zaki, MD). Ranibizumab 0.5 mg/0.05 ml was administered by intravitreal injection in full sterile precautions in the operating room.

Before injection, topical anesthesia was applied. Povidone iodine 5% was applied to eyelids, lashes, and conjunctival surface, and a lid speculum was placed.

Ranibizumab injections were injected 3.5 mm (in pseudophakic patient) 4.0 mm in (phakic patient) from the limbus to the vitreous cavity. The site of the injection was compressed using a cotton swab to prevent reflux as the needle was removed. Postoperatively, antibiotic (Ofloxacin) was applied topically for 7 days.

Imaging: all patients had EDI-OCT at baseline and after 3-month follow-up using the Heidelberg Spectralis. Subfoveal choroidal thickness (SFCT) was measured using the built-in caliper at a single point below the fovea extending from the bottom of the hyper-reflective layer corresponding to Bruch's membrane to the hyper-reflective layer at the sclerochoroidal junction. Central macular thickness was also recorded for all patients using OCT spectralis where images are generated by the fast volume scan: 20°×20° (6 × 6 mm) raster scans consisting of 25 horizontal lines. For each horizontal line, nine B-scans were averaged with the automatic real-time mode to reduce speckle noise. Only the scans with a numerical quality score of more than 16/40 db and in the blue range of the quality bar were collected, whereas scans with significant image artifacts were excluded.

The retinal thickness in each frame was calculated as the distance between the first signal from the vitreoretinal interface and the signal from the outer border of the retinal pigment epithelial (RPE). Spectralis OCT provides a circular map analysis in which the average thickness is displayed as a color code or numeric values in the nine Early Treatment Diabetes Retinopathy Study areas. The Early Treatment Diabetes Retinopathy Study map consists of three concentric rings with diameters of 1 mm (central), 3 mm (inner), and 6 mm (outer). The inner and outer rings are divided into four areas.

Statistical analysis: data were collected, tabulated, and statistically analyzed using an IBM personal computer with the Statistical Package for the Social Sciences (SPSS) version 22 (SPSS Inc., Chicago, Illinois, USA).

Student's (t-test) was used for comparison between two groups having quantitative variables. Mann–Whitney test (nonparametric test) was used for comparison between two groups not normally distributed having quantitative variables. Paired t-test was used for comparison between two related groups having quantitative variables. Wilcoxon signed-rank test (nonparametric test) was used for comparison between two related groups not normally distributed having quantitative variables. Logistic regression was used to calculate the effects of risk factors as independent odds ratios, while the effects of other confounders were removed. Pearson's correlation (r) was used to measure the association between quantitative variables.

P value greater than 0.05 was considered statistically nonsignificant. P value less than 0.05 was considered statistically significant. P value of less than 0.001 was considered statistically highly significant.

Results

Forty eyes from 40 patients with CRVO were included. Patients were classified into two groups according improvement in visual acuity, responder group in whom visual acuity gain greater than or equal to two lines and the nonresponder group in whom visual acuity gain less than two lines.

The mean age of functional responders was 57.7 ± 5.61 years, which was significantly younger than the nonresponders 61.5 ± 5.08 years (P = 0.034). There was no statistically significant difference between responders and nonresponders regarding their sex (P = 0.292) and presence of diabetes (P = 0.085) and hypertension (P = 0.085) [Table 1].

Table 1: Comparison between responder and nonresponder groups regarding their demographic data (n=40)

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Mean SFCT at baseline was 259.2 ± 37.9 μm in the functional responder group, which was greater than in nonresponders (224.9 ± 33.6 μm) (P = 0.005). Also, initial choroidal thickness in CRVO eyes of responders was significantly thicker than their corresponding fellow eye (202.5 ± 21.8 μm) (P = 0.001), whereas baseline choroidal thickness in nonresponder CRVO eyes (224.9 ± 33.6) was similar to their fellow eyes (221.2 ± 64.8 μm) (P = 0.840) [Table 2].

Table 2: Comparison between responder and nonresponder groups regarding their baseline subfoveal choroidal thickness in fellow eyes and study eyes (n=40)

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Postoperatively, mean SFCT significantly decreased for functional responders (207.3 ± 17.3 μm) (P < 0.001) but not for functional nonresponders (220.2 ± 41.1 μm) (P = 0.711) [Table 3].

Table 3: Comparison between responder and nonresponder regarding their baseline subfoveal choroidal thickness in the study eye and postoperative subfoveal choroidal thickness (n=40)

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Mean baseline BCVA for functional responders was 0.05 ± 0.00, which was similar to nonresponders 0.06 ± 0.01 (P = 0.333). Postoperatively, BCVA improved to 0.13 ± 0.04 (P < 0.001) in responders, but there was no improvement in BCVA for nonresponders 0.06 ± 0.02 (P = 0.180) [Table 4].

Table 4: Comparison between responder and nonresponder groups regarding their baseline and postoperative best-corrected decimal chart visual acuity in the study eye (n=40)

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There is positive correlation between postoperative SFCT and CMT and BCVA (P = 0.001) [Table 5].

Table 5: Correlation between changes in choroidal thickness and changes in best-corrected visual acuity and central macular thickness postoperatively

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Baseline indicator for function response: Multivariate logistic regression demonstrates that age less than 60 years was a positive predictor for functional response [odds ratio (OR)=2.39; P = 0.036] Also, baseline SFCT greater than 237 μm was a positive predictor for functional response (OR = 2.54; P = 0.025) [Table 6].

Table 6: Multivariate logistic regression for detection of baseline predictors of functional response among the studied group

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Discussion

CRVO is one of the most common vascular disorders of the retina. Choroidal thickness increased in CRVO due to retinal ischemia which increases the level of VEGF and leads to increased permeability of choroid vessels^[9].

Anti-VEGF is the first line of treatment in macular edema secondary to CRVO as it reduces the level of VEGF and hence choroidal vessel permeability^[10].

Increased initial thickness of the choroid can be a prognostic indicator for functional improvement of CRVO patients to anti-VEGF therapy as the thicker choroidal thickness can supply better perfusion to the outer layers of the retina. Also, thicker baseline choroid thickness means that macular edema is due to an increase of intraocular VEGF level, so response to anti-VEGF can be predicted, while thinner choroidal thickness means less affected choroid by VEGF and hence decreases the response to anti-VEGF therapy^[4]. In fact, many studies correlate between choroidal thickness at baseline and functional improvement after anti-VEGF therapy in many diseases such as diabetic macular edema and age-related macular degeneration and they found that a higher baseline choroidal thickness correlated with favorable functional and anatomic outcome^[11],[12]. In our study, the mean SFCT at baseline was (259.2 ± 37.9 μm) in the functional responder group, which was thicker than in nonresponders (224.9 ± 33.6 μm; P = 0.005). Also, initial choroidal thickness in CRVO eyes of responders was significantly thicker than their normal fellow eye (202.5 ± 21.8 μm; P = 0.001), whereas choroidal thickness at baseline in nonresponder CRVO eyes (224.9 ± 33.6) was similar to their normal fellow eye (221.2 ± 64.8 μm; P = 0.840).

In addition to that, multivariate logistic regression demonstrates that baseline SFCT greater than 237 μm was a positive indicator for functional improvement (OR = 2.54; P = 0.025).

Furthermore, there is positive correlation between postoperative SFCT and CMT and BCVA (P = 0.001).

Similar to our study, Rayess et al.^[4] studied 42 CRVO eyes and found that choroidal thickness at baseline in CRVO eyes (246 ± 102 μm) was greater than their normal fellow eye (197 ± 86 μm) and the mean of choroidal thickness for patients who respond to anti-VEGF therapy (272.2 ± 107.3 μm) was greater than mean choroidal thickness in patients who did not respond to therapy (209.6 ± 85.8 μm). Tsuiki et al.^[5] studied 36 CRVO eyes and found that choroidal thickness in CRVO eyes (257.1 ± 83.2 μm) was greater than their normal fellow eye (222.6 ± 67.8 μm). Lee et al.^[6] studied 42 retinal vein occlusion eyes and also found that initial choroidal thickness in RVO eyes was greater than their normal fellow eye. In contrast, Du et al.^[7] found that there is no difference between choroidal thickness in RVO eyes and their normal eye.

This difference between our study and DU study could be due to the type of selected patients as in DU the patients were not newly diagnosed as the patient did not have macular edema in their optical coherence tomography images, while in our study all patients were newly diagnosed CRVO with secondary macular edema. In addition to that, in our study multivariate logistic regression demonstrates that age less than 60 years was a positive indicator for functional improvement in CRVO patients (OR = 2.39; P = 0.036). Although in our study we did not assess whether patients had perfusion or nonperfusion CRVO, this may be due to that older patients usually had nonperfusion CRVO. Also, studies found that increasing age is associated with a decrease in choroidal thickness^[13].

Our study has several limitations. First, follow-up of the patient and data collected was at 3 months after anti-VEGF therapy. We do not know if this is data still the same after more follow-ups. So longer studies for 6 months or more could be helpful to determine validity of this data. Second, in our study we used Ranibizumab as anti-VEGF. Another anti-VEGF could produce different result. A larger study including comparison between all types of anti-VEGF and their effect on choroidal thickness may give valuable result. Finally, our study did not assess whether patient had perfusion or nonperfusion type of CRVO which could influence the result as older patients usually had nonperfusion CRVO which significantly affects the outcome of the disease.

Conclusion

There are changes that occur in the choroid thickness during the pathological process of CRVO. Eyes with CRVO have greater choroidal thickness than their normal fellow eyes. Patients with CRVO and their age less than 60 years old have favorable outcome when treated with 3 months anti-VEGF therapy. In addition, a thicker initial choroidal thickness in CRVO patient in comparison with his normal eye could be a prognostic indicator for functional improvement after 3 months of anti-VEGF therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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