Etiology and pathogenesis

During embryonic development of the eye, the compartment between the retina and crystalline lens contains a vascular system (hyaloid artery) that provides nutrients for the developing eye. The hyaloids vessels and the primary vitreous are supposed to regress in the third trimester of pregnancy.

PHPV may be due to a defect in the regression of the primary vitreous or in the formation of the secondary vitreous (that fills the developing second eye and is derived from the inner retinal cells starting in the 9th week of gestation) or to a combination of both. The persistent hyaloid vasculature and mesenchymal tissue from the embryonic primary vitreous in a microphthalmic eye leads to the clinical spectrum of PHPV. The exact cause and pathogenetical mechanisms, however, remain poorly understood.

In some patients with PHPV, mutations in the NDP gene have been identified. NDP mutations have been associated with a spectrum of pediatric retinal vitreopathies. Among them, Norrie disease represents the most severe phenotype, while PHPV together with X-linked familial exudative vitreoretinopathy (FEVR), Coats disease and retinopathy of prematurity (ROP) represent the less severe phenotypes.

The pathogenetic role of the NDP mutations in PHPV was supported by findings in Ndp knockout animal models that demonstrated failure of the primary hyaloid artery and associated structures to regress. One patient with bilateral PHPV was reported to have a mutation the NDP gene and the mother of this patient was confirmed to be a carrier.