Alterations in choroidal vascular structures due to serum levels of vascular endothelial growth factor in patients with POEMS syndrome

Abstract

A higher serum vascular endothelial growth factor (VEGF) level can cause choroidal thickening in the choroid of patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. We aimed to determine whether fluctuations in serum VEGF levels affect choroidal vascular structures in patients with POEMS syndrome. This retrospective observational case series examined 17 left eyes of 17 patients with POEMS syndrome. Enhanced depth imaging optical coherence tomography (EDI-OCT) images were obtained, and serum VEGF levels were measured at baseline and 6 months after transplantation with dexamethasone (n = 6), thalidomide (n = 8), or lenalidomide (n = 3). EDI-OCT images were binarized using ImageJ software, and we calculated the areas of the whole choroid and the luminal and stromal areas. Subsequently, we determined whether the choroidal vascular structure had changed significantly between baseline and 6 months after treatment. Six months after treatment, serum VEGF levels and the whole choroid, luminal, and stromal areas had decreased significantly compared to the baseline values (all, P < 0.001). The mean luminal area to the whole choroidal area ratio at 6 months after treatment was 0.70 ± 0.03, which was significantly smaller than the ratio at baseline (0.72 ± 0.03; P < 0.001). Whole choroid and luminal area fluctuations were significantly positively correlated with fluctuations in serum VEGF levels (r = 0.626, P = 0.007 and r = 0.585, P = 0.014, respectively). Choroidal thickening induced by VEGF might be caused by increases in the choroidal vessel lumen area. These results may offer insights into the pathogenesis of POEMS syndrome and the role of serum VEGF in choroidal vascular structure, which may apply to other ocular diseases.

Figure 1

Choroidal structure analysis via enhanced depth imaging (EDI) optical coherence tomography (OCT). An EDI-OCT image was converted to a binary image using ImageJ software (Bethesda, MD). The luminal choroidal area and the stroma choroidal area are seen in this image. The rectangle surrounded by a red line was excised, and the dark areas were traced using the Niblack method. In this situation, EDI-OCT images were gained in the macular area via horizontal sectioning (the optic disc is localised on the left side). A 1500-μm area covering the fovea was segmented and analysed in this study. The whitish and blackish regions correspond to the stromal and luminal areas, respectively. EDI-OCT images (left eye) of the 42-year-old female patient with POEMS syndrome reported reveals a choroidal thickening at baseline (a,b) and choroidal thinning 6 months post-treatment (c,d). An EDI-OCT image was converted to a binary image using the Niblack method, available within ImageJ software. (a) EDI-OCT image of left eye at baseline (b) Converted binary image of EDI-OCT image of left eye at baseline (c) EDI-OCT image of left eye 6 months post-treatment (d) Converted binary image of EDI-OCT image of left eye 6 months post-treatment.

Figure 2

Correlations between fluctuations in whole choroidal and luminal areas and in serum VEGF (vascular endothelial growth factor). (A) Correlation between fluctuations in the whole choroidal area and in serum VEGF levels in the left eye. The whole choroidal area significantly decreased along with serum VEGF levels (r = 0.626, P = 0.007, Spearman’s rank correlation coefficient). (B) Correlations between fluctuations in the luminal area and in the serum VEGF levels in the left eye. The luminal choroidal area was decreased significantly along with a reduction in serum VEGF levels, and the correlation between fluctuations in the luminal area and in serum VEGF levels in patients with POEMS syndrome was significant (r = 0.585, P = 0.014, Spearman’s rank correlation coefficient).

Figure 3

Correlations between fluctuations in luminal and stroma areas and in whole choroidal area. (A) Correlations between fluctuations in luminal area and in the whole choroidal area. There was a significant correlation between fluctuations in luminal area and in whole choroidal area in patients with POEMS syndrome (r = 0.963, P < 0.001, Spearman’s rank correlation coefficient). (B) Correlations between fluctuations in the stromal area and in the whole choroidal area. There was a significant correlation between fluctuations in luminal area and in the whole choroidal area in patients with POEMS syndrome (r = 0.797, P < 0.001, Spearman’s rank correlation coefficient).