Clinical features, etiology and pathogenesis

Clinical features

ROP usually develops in both eyes. Ocular findings include retinal neovascularization, fibrous proliferation and end-stage retrolental fibroplasia, progressing towards partial and complete retinal detachment and blindness. Severe damage may lead to retinal folds involving the macula and macula ectopia and phthisis bulbi

Clinical features that are mostly present in severe and untreated ROP are myopia, amblyopia, strabismus, nystagmus, glaucoma, cataracts. Retinal detachment is the main cause of total blindness in ROP.

Etiology and pathogenesis

ROP refers to damage to the blood vessels of the developing eye. Normally, the blood vessels of the retina begin to develop 3 months after conception and achieve a complete development at the time of normal birth. In preterm infants, however, the vessel growing is disrupted. This gives rise to development of abnormal vessels and fibrovascular proliferation that can lead to vitreoretinal traction and retinal detachment.

The etiology of ROP appears to be multifactorial. The role of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) that are critical to normal vascular development is under extensive investigation.

There are clear evidences that genetic susceptibility plays an important pathogenetical role but the exact mechanisms involved remain to be elucidated. ROP involves retinal changes similar to those found in familial exudative vitreoretinopathy (FEVR), Norrie disease and Coats disease. Mutations in the NDP gene on chromosome Xp11.4 were identified not only in Norrie disease and X-linked FEVR but also in premature infants with advanced ROP. The NDP gene encodes for the 133 amino acids protein Norrin, which acts as a ligand in a Wnt receptor-β-catenin signal transduction pathway. The latter plays a regulatory role in retina development and is necessary for regression of hyaloid vessels in the eye. No phenotype-associated NDP mutations have been identified so far. Despite some controversies on the importance of the NDP gene in the pathogenesis of ROP, NDP mutations may account for at least a proportion of advance cases of ROP.