Incontinentia pigmenti is a rare X-linked disorder that affects the eyes, central nervous system, skin, and teeth.1,2 Ocular abnormalities are seen in approximately 35% of patients3 and include conjunctival pigmentation, strabismus, cataracts, optic atrophy, and retinal abnormalities.2 The main retinal findings include macular capillary dropout, peripheral avascularity, arteriovenous anastomoses at the junction of the vascular and avascular retina, preretinal neovascularization, and retinal detachment.1 We now report 2 cases of persistence of fetal vasculature (PFV) in the eyes of patients with incontinentia pigmenti.
An 8-month-old female infant was referred from the Department of Dermatology with the diagnosis of incontinentia pigmenti having been made 1 month prior to our initial examination. The family history was unremarkable. She was the product of a full-term vaginal delivery and had no neonatal oxygen therapy. She was healthy except for the presence of an erythematous vesicular rash since birth. An irregular pupil had been noted in the right eye since age 6 months. She did not respond to a bright light shining in the right eye but was able to fix and follow objects with the left eye. Iridohyaloid vessels (signs of PFV)4 were present in the right eye at the 1-o'clock and 10-o'clock meridians. The anterior chamber was formed and deep. A posterior synechia was observed at the 2-o'clock meridian. A dense white retrolental plaque did not allow a view of the fundus. Findings from ultrasonography of the right eye revealed a thin threadlike echogeneic density extending from the disc to the retrolental space, probably representing a hyaloid artery or its remnant (Figure 1). There was no evidence of intravitreal blood or retinal detachment. A diagnosis was made of persistent hyperplastic primary vitreous, also known as persistent fetal vasculature.4 The patient underwent examination under general anesthesia with fluorescein angiography at 9 and 12 months of age. The anterior segment of the left eye was normal. The posterior pole of the left eye appeared normal on ophthalmoscopy, although an irregularity of the foveal avascular zone was present on the fluorescein angiogram. Examination of the retinal periphery of the left eye disclosed widespread areas of peripheral nonperfusion, with a scalloped preretinal whitish tuft present at the equator in the 2-o'clock meridian. The angiographic evidence of leakage in the area of the white preretinal tissue supported the clinical impression of the presence of neovascularization (Figure 2). Findings from ultrasonography of the right eye, repeated at 9 months of age, revealed evidence of dense retrolental blood and fibrous tissue and a total tractional retinal detachment (Figure 3). The axial lengths were 17 mm OD and 19 mm OS.
Case 1. Top, Ultrasonogram of the right eye at 8 months of age reveals a threadlike echogeneic density extending from the disc to the retrolental space (between the arrows), representing a hyaloid artery; on indicates optic nerve. Bottom, Artist's depiction.
Case 1. Fluorescein angiogram of the left eye reveals leakage in an area of scalloped preretinal whitish tuft at the equator that is consistent with neovascularization.
Case 1. Ultrasonogram of the right eye at 9 months of age reveals total retinal detachment surrounding Cloquet canal (arrow) and subretinal dispersed blood (asterisk).
Results of ultrasound examination at 12 months of age disclosed total retinal detachment and dense organization of the vitreous in the right eye. The axial length of the right eye had decreased to 16.1 mm, consistent with phthisis. The examination of the left eye remained unchanged at 12 months of age.
A 23-year-old woman with a diagnosis of incontinentia pigmenti was referred for the management of retinal detachment in her left eye. Her mother and sister also had incontinentia pigmenti. She was the product of a full-term uncomplicated vaginal delivery and had no neonatal oxygen therapy. The patient had been noted to have persistent hyperplastic primary vitreous in the right eye at 3 months of age. The visual acuity, at the present examination, was no light perception OD and 20/20 OS. Findings from slitlamp examination of the right eye disclosed an iridohyaloid blood vessel4 and a white pupil with a cataractous lens. Iris bombe was present for 360°. A Mittendorf dot (a common sign of PFV)4 was present in the left eye. The anterior segment in the left eye was otherwise normal. A macula-attached rhegmatogenous retinal detachment was detected inferonasally in the left eye. The patient underwent a successful scleral buckling procedure.
These 2 cases illustrate the simultaneous occurrence of 2 distinct and rare diseases with intraocular vascular abnormalities. This association of incontinentia pigmenti with PFV (in various stages of maturation) has been previously described in 3 patients.5- 7 Zweifach5 reported the presence of an iridohyaloid artery in a patient with incontinentia pigmenti. Pollard6 described a child with incontinentia pigmenti and a "combination of anterior and posterior PHPV." A persistent hyaloid artery in a case of incontinentia pigmenti was also described in the German literature by von Krummel and Rausch.7 The PFV in incontinentia pigmenti may thus be more prevalent than previously believed.
The exact relationship between these rare coexisting diseases is not clear, but it may not necessarily be one of chance. Persistence of fetal vasculature has been associated with various neonatal states of abnormal or deficient retinal vascularization. These disorders include Norrie disease, retinopathy of prematurity, prematurity per se (without retinopathy of prematurity), and familial exudative vitreoretinopathy.4 Retinal vascular insufficiency is a feature common to all of these disorders, including incontinentia pigmenti.1,3 The poorly vascularized, ischemic retina in these conditions may possibly elaborate angiogenic factors that facilitate PFV, which, in the absence of such factors, would ordinarily involute prior to birth.
Ischemic retina in various diseases, including retinopathy of prematurity, induces the production of vascular endothelial growth factor.8 During intrauterine development, retinal ischemia in patients with incontinentia pigmenti, and in the other conditions noted above, may trigger the production, up-regulation, or abnormal persistence of an angiogenic factor such as vascular endothelial growth factor. The endothelial growth factor may then directly support PFV, or, by down-regulating other factors responsible for the atrophy of the fetal hyaloid vascular system, prevent or retard its regression. Such an imbalance between vasoinhibitory and vasostimulatory growth factors has been proposed as an explanation for the lack of vascular regression in some cases of PFV.4 If such an explanation proves to be valid for incontinentia pigmenti, it suggests that the genetic abnormality causing retinal ischemia exerts its effects at an early stage of gestation before the spontaneous involution of fetal vessels normally occurs.
Many patients with incontinentia pigmenti develop funnel-shaped retinal detachments or phthisic eyes. It is usually assumed that such end-stage manifestations of the disease are secondary to preretinal neovascularization that leads to vitreous hemorrhage and subsequent tractional retinal detachment. This proposed sequence of events may well be valid in some patients. However, as may have been the course in case 1, a similar end point could be reached by bleeding from persistent fetal vessels within the vitreous chamber. Persistence of fetal vasculature, triggered by retinal ischemia, may be a previously unnoticed mechanism of blindness in patients with incontinentia pigmenti.
Corresponding author: Jeffrey S. Heier, MD, Retina Vitreous Associates, 7305 W Jefferson Blvd, Fort Wayne, IN 46804.
Fard AK, Goldberg MF. Persistence of Fetal Vasculature in the Eyes of Patients With Incontinentia Pigmenti. Arch Ophthalmol. 1998;116(5):682–684. doi:
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