Balmer and Munier Figure 4 (a) Total retinal detachment in a 2 month-old boy. (b) Corresponding ultrasonography showing an intraocular mass with high reﬂectivity (calciﬁcations) and marked attenuation (shadowing) characteristic for retinoblastoma. The primary lesion is most likely a localized, evolutive abnormality of the developing retinal vessels. The precise origin remains unknown, but Coats’ disease may be linked to a somatic mutation of the NDP gene (Norrie Disease Protein) leading to a deﬁciency of norrin in the developing retina (Black et al 1999). Persistent hyperplastic primary vitreous (PHPV) or persistence of the fetal vasculature (PFV) Coats’ disease and persistence of Persistent Hyperplastic Primary Vitreous are the most common benign lesions to mimic retinoblastoma (Reese 1955; Goldberg 1997). PHPV is a congenital malformation caused by the arrest of normal regression of the embryonic vascular connective tissue (hyaloid artery, vasa hyaloidea propria, tunica vascu- losa lentis), regression that normally occurs after 4 months gestation. Almost always unilateral, this condition often presents with moderate microphthalmia and other associated 436 malformations such as failure of cleavage of the anterior segment or uveal coloboma. PHPV is non hereditary. The most common signs and symptoms are leukocoria, this caused by retrolental ﬁbroplasia and/or cataract, microph- thalmia and characteristic traction of the ciliary processes sometimes visible in the periphery of the dilated pupil. Clinical manifestations of PHPV are varied and numer- ous, affecting the anterior and/or posterior segments, rang- ing from minimal isolated lesions to complex interactive secondary complications. The natural course of the disease may result in early cataract and closed-angle glaucoma. In the long term, enucleation may be inevitable due to terminal glaucoma, intra-ocular hemorrhage, retinal detachment, uveitis or phthisis bulbi. Retinopathy of prematurity (ROP) Retinopathy of prematurity, known previously as retrolen- tal ﬁbroplasia, results from the abnormal proliferation of retinal vessels, for the most part in premature infants with a birthweight less than 1250 gm or of under 32 weeks gesta- tion. These children have usually received oxygen therapy, and the ﬁrst signs of retinopathy appear between 35 and 45 post-conceptional weeks. In the vast majority of cases spon- taneous regression occurs over a period of 3 to 4 months. Only children of under 1000 gm birthweight are threatened with blindness. The ﬁrst and earliest clinical feature is a clear line of demarcation between the vascular and avascular retina (stage 1) (Anon 1987), indicating that angiogenesis is slow- ing down or even arrested. Angiogenesis starts around the 16th week of gestation and normally terminates at 36 weeks for the nasal retina, at term for the temporal retina. Capillary growth on the line of demarcation forms a prominent ridge (stage 2), a neoproliferation that may reach beyond the retina, inﬁltrating the internal limiting membrane and extending into the vitreous (stage 3). At this stage it forms a dense ﬁbrovascular membrane reaching from front to back of the vitreous body and may cause retraction of arborized vessels to form a falciform fold, papillary dysversion and macular ectopia. Unchecked, traction from the proliferation will cause initially a partial retinal detachment (stage 4), ultimately a total detachment (stage 5), ﬁnally resulting in the cicatricial stage of retrolental ﬁbroplasia. Leukocoria may be present from stage 3 onwards. The retinopathy may arrest spontaneously at any point of the natural course of the disease, the critical period being the stage when neovascularization invades the vitreous, the Clinical Ophthalmology 2007:1(4)