Clinicopathological findings in refractory diabetic macular edema: A case report

Abstract

The present study describes the case of a patient with refractory diabetic cystoid macular edema who underwent vitrectomy with en bloc removal of the cystoid lesion component. The current study also performed histopathological and immunohistochemical analyses of the cystoid lesion component to assess fibrin/fibrinogen and advanced glycation end-products (AGEs) immunoreactivity. A 69-year-old Japanese man presented with visual loss in the left eye due to residual cystoid macular edema (CME) refractory to anti-vascular endothelial growth factor therapy. Best-corrected visual acuity was 1.2 in the right eye (OD) and 0.5 in the left eye (OS). Fundus examination showed dot hemorrhages and hard exudates in the peri-macular region with pan-retinal photocoagulation scars in both eye. Swept-source optical coherence tomography revealed CME with slight hyperreflectivity in the cyst OS. A total of 3 months after the initial visit, pars plana vitrectomy was performed, and the translucent solidified component within the cystoid lesion was isolated. Histopathologically, the excised component was elliptical in shape, measuring 0.7x0.4 mm and exhibited homogeneous eosinophilic material without cellular components. No membranous structure was observed surrounding the component. Immunohistochemistry demonstrated that the tissue was positive for fibrin/fibrinogen and weakly positive for AGEs, but was negative for glial fibrillary acidic protein, type 1 collagen and receptor for AGEs. To the best of our knowledge, the present case report is the first to histopathologically examine the contents of refractory CME, and to immunohistochemically demonstrate that fibrin in diabetic CME may be post-translationally modified by AGEs. These results suggested that fibrin in CME may escape degradation by plasmin due to post-translational modifications.

Keywords: advanced glycation end-products; diabetic cystoid macular edema; fibrin clot; post-translational modification.

Figure 1

Clinical findings in the present case of diabetic cystoid macular edema. (A) Color fundus photography showed the dot hemorrhage and hard exudates at the peri-macular region in the left eye. (B) Swept-source optical coherence tomography at the horizontal section revealed the presence of spongiform edema with cystoid space in the macula. (C) Cystotomy of the cystoid macular lesion revealed a translucent solid component. (D) The excised cystoid lesion component was soft and solid.

Figure 2

Histopathological findings of the excised tissue (hematoxylin and eosin staining). (A) The excised tissue was elliptical in shape, measuring 0.7x0.4 mm, and displayed a homogeneous structure comprising eosinophilic material without cellular components. Scale bar, 100 µm. (B) A few erythrocyte aggregates were observed at the margin of the component (black arrows). Scale bar, 20 µm.

Figure 3

Findings of fluorescence immunohistochemistry and bright-field microscopic imaging of the excised tissue. (A-D) Bright-field microscopic imaging corresponds to the respective images as follows: (A) corresponds to (E), (B) corresponds to (F), (C) corresponds to (G), and (D) corresponds to (H). Bright-field microscopic images of (E-H), respectively. Immunohistochemical staining was (E) strongly positive for fibrin/fibrinogen, (F) weakly positive for AGEs, and (G) negative for type 1 collagen. (H) Immunohistochemistry staining of the negative control rabbit IgG. Scale bar, 50 µm. AGEs, advanced glycation end-products.