Choroidal Thickness After Dexamethasone Implant in RVO
Choroidal Thickness After Dexamethasone Implant in RVO
This study demonstrated that choroidal thickness in RVO eyes with MO was higher than it was in normal contralateral eyes. In addition, injection of an intravitreal dexamethasone implant decreased both choroidal thickness and central retinal thickness. After Ozurdex injection, the mean CMT gradually increased from month 3 and the mean SFCT increased from month 5. These results suggest that a change in choroidal thickness follows a change in retinal thickness, and they also suggest that it is a change in the retina that accounts for choroidal thickening in eyes with RVO.
Mean SFCT, as measured by Tsuiki et al in eyes with CRVO, was 257.1±83.2 μm, which was greater than that in normal contralateral eyes (222.6±67.8 μm). Mean SFCT decreased from 266.9±79.0 to 227.7±65.1 μm after intravitreal bevacizumab injection. In this study, mean SFCT in eyes with RVO was 260.3±71.2 μm, which was greater than that in normal contralateral eyes (217.6±55.3 μm). After Ozurdex injection, these values decreased to 239.0±73.8 and 228.2±63.1 μm at 1 and 3 months, respectively. This finding, which even included eyes with BRVO, was consistent with the findings of Tsuiki et al. In contrast, there is a contradictory report on choroidal thickness in eyes with RVO. The Beijing Eye Study, a population-based, cross-sectional study that was conducted in northern China, showed that there was virtually no difference in SFCT in eyes with RVO and normal contralateral eyes. This discrepancy between the Beijing Eye Study and our study may be explained by the difference in baseline patient characteristics. All eyes in our study exhibited recently developed RVO with MO, whereas in the Beijing Eye Study there was no instance of marked cystoid MO on OCT images and no case of recent-onset RVO. However, the Beijing Eye Study and our study did yield the similar finding that the SFCT in eyes with BRVO and eyes with CRVO did not significantly differ. The reason for the finding that no significant difference in SFCT existed between eyes with BRVO and eyes with CRVO is unclear, but it could be attributed to the effects of several relatively severe cases of BRVO with considerable MO in our study.
Although the exact mechanism that causes an increase in choroidal thickness in eyes with RVO and a decrease in choroidal thickness after Ozurdex injection was not determined, we hypothesised the following: The choriocapillaris has fenestrations that allow for the outflow of large molecules and increases the amount of material leaving the capillaries. Soluble VEGF isoforms can increase vascular permeability and induce fenestrations of the choriocapillaris. In hypoxic RVO eyes, VEGF expression is increased in retinal endothelial cells, pericytes, RPE, Müller cells, ganglion cells and astrocytes. VEGF induces choroidal vascular hyperpermeability, which in turn increases choroidal thickness. Choroidal thickening is also mediated by the vascular dilation induced by nitric oxide production, which in turn is triggered by VEGF expression. All of these factors can cause vasodilation and oedema that can then lead to choroidal thickening. Meanwhile, McAllister et al demonstrated that triamcinolone downregulates VEGF expression and also inhibits an increase in the expression of glial fibrillary acidic protein, a protein associated with retinal vascular permeability, in an animal model of BRVO. Corticosteroids are also known to reduce tissue oedema and inhibit the synthesis of endothelial nitric oxide synthase. The mechanism by which the intravitreal dexamethasone implant reduces choroidal thickness in eyes with RVO may involve a similar pathway.
While the correlation between the SFCT and CMT ratios at baseline was not significant, the correlations between these two ratios were significant at 3 and 5 months after Ozurdex injection. Additionally, the changes in SFCT and CMT at 3 and 5 months after Ozurdex injection correlated significantly in this study. Our results suggest that even though the degree of retinal thickening at baseline does not necessarily reflect the choroidal thickening in eyes with acute-onset RVO, the responsiveness of these two layers to corticosteroid do correlate with each other. Our study also showed that the serial changes of retinal and choroidal thicknesses in RVO eyes treated with Ozurdex were different, demonstrating delayed response of choroid to Ozurdex. At this time, it is unclear why the choroidal thickness decreases slower than the retinal thickness after Ozurdex injection. Meanwhile, the slower change of choroidal thickness over 3 months is comparable to that of visual improvement after Ozurdex injection in our study. The GENEVA Study reported that visual acuity continued to improve over 3 months after Ozurdex injection, suggesting that factors other than changes in central retinal thickness may be affecting visual acuity in RVO eyes treated with Ozurdex. Choroidal thickness might be considered as one of the factors. Based on the fact that the choroid plays an important role in maintaining the RPE and the outer retina, the choroid is considered important for visual acuity. Eyes with a relatively thicker choroid at baseline may have more choroidal blood supply and choriocapillaris, which could increase the possibility of recovery after corticosteroid treatments.
This study has several limitations. First, the sample size was small and the follow-up periods were short. Further studies with increased patient numbers and a longer follow-up duration will be needed to confirm our results. Second, manual measurements of choroidal thickness always have a potential bias. Automated software is required for a more objective and definitive evaluation.
In conclusion, SFCT in eyes with RVO is significantly greater than in normal contralateral eyes. Injection of an intravitreal dexamethasone implant results in reduction of choroidal thickness and also leads to the resolution of MO. The improvement in visual acuity was significantly correlated with a decrease in SFCT after Ozurdex injection.
Discussion
This study demonstrated that choroidal thickness in RVO eyes with MO was higher than it was in normal contralateral eyes. In addition, injection of an intravitreal dexamethasone implant decreased both choroidal thickness and central retinal thickness. After Ozurdex injection, the mean CMT gradually increased from month 3 and the mean SFCT increased from month 5. These results suggest that a change in choroidal thickness follows a change in retinal thickness, and they also suggest that it is a change in the retina that accounts for choroidal thickening in eyes with RVO.
Mean SFCT, as measured by Tsuiki et al in eyes with CRVO, was 257.1±83.2 μm, which was greater than that in normal contralateral eyes (222.6±67.8 μm). Mean SFCT decreased from 266.9±79.0 to 227.7±65.1 μm after intravitreal bevacizumab injection. In this study, mean SFCT in eyes with RVO was 260.3±71.2 μm, which was greater than that in normal contralateral eyes (217.6±55.3 μm). After Ozurdex injection, these values decreased to 239.0±73.8 and 228.2±63.1 μm at 1 and 3 months, respectively. This finding, which even included eyes with BRVO, was consistent with the findings of Tsuiki et al. In contrast, there is a contradictory report on choroidal thickness in eyes with RVO. The Beijing Eye Study, a population-based, cross-sectional study that was conducted in northern China, showed that there was virtually no difference in SFCT in eyes with RVO and normal contralateral eyes. This discrepancy between the Beijing Eye Study and our study may be explained by the difference in baseline patient characteristics. All eyes in our study exhibited recently developed RVO with MO, whereas in the Beijing Eye Study there was no instance of marked cystoid MO on OCT images and no case of recent-onset RVO. However, the Beijing Eye Study and our study did yield the similar finding that the SFCT in eyes with BRVO and eyes with CRVO did not significantly differ. The reason for the finding that no significant difference in SFCT existed between eyes with BRVO and eyes with CRVO is unclear, but it could be attributed to the effects of several relatively severe cases of BRVO with considerable MO in our study.
Although the exact mechanism that causes an increase in choroidal thickness in eyes with RVO and a decrease in choroidal thickness after Ozurdex injection was not determined, we hypothesised the following: The choriocapillaris has fenestrations that allow for the outflow of large molecules and increases the amount of material leaving the capillaries. Soluble VEGF isoforms can increase vascular permeability and induce fenestrations of the choriocapillaris. In hypoxic RVO eyes, VEGF expression is increased in retinal endothelial cells, pericytes, RPE, Müller cells, ganglion cells and astrocytes. VEGF induces choroidal vascular hyperpermeability, which in turn increases choroidal thickness. Choroidal thickening is also mediated by the vascular dilation induced by nitric oxide production, which in turn is triggered by VEGF expression. All of these factors can cause vasodilation and oedema that can then lead to choroidal thickening. Meanwhile, McAllister et al demonstrated that triamcinolone downregulates VEGF expression and also inhibits an increase in the expression of glial fibrillary acidic protein, a protein associated with retinal vascular permeability, in an animal model of BRVO. Corticosteroids are also known to reduce tissue oedema and inhibit the synthesis of endothelial nitric oxide synthase. The mechanism by which the intravitreal dexamethasone implant reduces choroidal thickness in eyes with RVO may involve a similar pathway.
While the correlation between the SFCT and CMT ratios at baseline was not significant, the correlations between these two ratios were significant at 3 and 5 months after Ozurdex injection. Additionally, the changes in SFCT and CMT at 3 and 5 months after Ozurdex injection correlated significantly in this study. Our results suggest that even though the degree of retinal thickening at baseline does not necessarily reflect the choroidal thickening in eyes with acute-onset RVO, the responsiveness of these two layers to corticosteroid do correlate with each other. Our study also showed that the serial changes of retinal and choroidal thicknesses in RVO eyes treated with Ozurdex were different, demonstrating delayed response of choroid to Ozurdex. At this time, it is unclear why the choroidal thickness decreases slower than the retinal thickness after Ozurdex injection. Meanwhile, the slower change of choroidal thickness over 3 months is comparable to that of visual improvement after Ozurdex injection in our study. The GENEVA Study reported that visual acuity continued to improve over 3 months after Ozurdex injection, suggesting that factors other than changes in central retinal thickness may be affecting visual acuity in RVO eyes treated with Ozurdex. Choroidal thickness might be considered as one of the factors. Based on the fact that the choroid plays an important role in maintaining the RPE and the outer retina, the choroid is considered important for visual acuity. Eyes with a relatively thicker choroid at baseline may have more choroidal blood supply and choriocapillaris, which could increase the possibility of recovery after corticosteroid treatments.
This study has several limitations. First, the sample size was small and the follow-up periods were short. Further studies with increased patient numbers and a longer follow-up duration will be needed to confirm our results. Second, manual measurements of choroidal thickness always have a potential bias. Automated software is required for a more objective and definitive evaluation.
In conclusion, SFCT in eyes with RVO is significantly greater than in normal contralateral eyes. Injection of an intravitreal dexamethasone implant results in reduction of choroidal thickness and also leads to the resolution of MO. The improvement in visual acuity was significantly correlated with a decrease in SFCT after Ozurdex injection.
