Unilateral sporadic retinal dysplasia: results of histopathologic, immunohistochemical, chromosomal, genetic, and VEGF-A analyses.

PURPOSE: To describe new findings in a case of unilateral retinal dysplasia.
METHODS: Histopathologic evaluation of an enucleated globe and analysis with immunohistochemical probes, karyotyping, and genetic analysis for the Norrie gene, and aqueous assay for vascular endothelial growth factor A (VEGF-A).
RESULTS: Histopathological examination of the globe revealed retinal dysplasia with pseudorosette formation, abnormal or absent retinal nuclear lamination, a paucity of disorganized retinal microvasculature, retinal infoldings, advanced gliosis, persistent hyperplastic vitreous, exuberant neovascularization of the vitreous, and iris neovascularization (identical to the findings observed in bilateral Norrie disease). Immunohistochemistry disclosed GFAP-positive and GLUT-1-positive gliosis and retinal and persistent hyperplastic vitreous microvessels that were CD34-positive and GLUT-1-negative. Ki-67-positive retinal cells were polarized toward the subretinal space and absent in the retinal invaginations and pseudorosettes. A normal karyotype was found, and DNA sequencing revealed no known mutation in the region of the Norrie gene (NDP) in sputum or retinal DNA. Aqueous obtained immediately after enucleation contained an exceptionally high concentration of VEGF-A (4.5 ng/mL).
CONCLUSIONS: Despite the failure to find an abnormal NDP allele, other unexplored NDP regions, an undetected defect restricted to retinal tissues, or an autosomal mutation coupled with disrupted signaling pathways may be responsible for the condition. High aqueous VEGF-A suggests that this cytokine may play a role in pathogenesis in conjunction with other pathways.