Proliferative tissue filling a full-thickness macular hole secondary to proliferative diabetic retinopathy: a case report with clinicopathological analysis

Proliferative diabetic retinopathy (PDR) is characterized by neovascularization and fibrovascular proliferative tissue (FPT) in the setting of chronic ischemia. We herein report an extremely rare case of PDR-associated full-thickness macular hole (FTMH), in which proliferative tissue extended through and filled the FTMH. We describe the clinical course and histopathological findings of this case. A 52-year-old Japanese man with bilateral PDR presented with a whitish lesion at the fovea of his left eye. Optical coherence tomography revealed a hyperreflective lesion penetrating the full thickness of the retina. The patient underwent pars plana vitrectomy. Intraoperatively, FTMH was identified following the removal of the foveal FPT. The hole was successfully managed using the inverted ILM flap technique and gas tamponade, resulting in hole closure and visual improvement. Histopathological analysis of the removed tissue revealed collagenous tissue containing no identifiable retinal tissue, along with CD68-positive cells and Berlin blue-negative pigment-containing cells. Immunofluorescence showed positivity for SM22α, GFAP, and p-SMAD2. Notably, co-expression of GFAP and p-SMAD2 was observed, suggesting activation of the TGF-β signaling pathway in glial cells. This case demonstrates the detailed histopathological characteristics of collagenous tissue occupying the lumen of an FTMH secondary to PDR. Although the precise mechanism underlying its formation remains unclear, the pathological findings raise the possibility that mesenchymal transition via the TGF-β/SMAD pathway may have been involved in the formation of this tissue.