Chapter 145 – Persistent Fetal Vasculature Syndrome
A. BAWA DASS
MICHAEL T. TRESE
• A developmental ocular anomaly in which the primary vitreous and hyaloid vasculature fail to involute completely.
• Retrolenticular fibrovascular tissue.
• Elongated ciliary processes.
• Usually unilateral.
• Late-onset angle-closure glaucoma.
• Intraocular hemorrhage.
• Optic nerve hypoplasia.
• Retinal detachment.
Persistent fetal vascular syndrome (PFV) is an uncommon congenital ocular anomaly in which the hyaloid vasculature system and primary vitreous fail to involute. This was initially described in detail by Reese in his 1955 Jackson Memorial Lecture, at which time it was described as persistent hyperplastic primary vitreous (PHPV). Although the visual outcomes historically have been poor, advances in clinical evaluation and surgical technique have resulted in more frequent preservation of the affected eyes and vision.
EPIDEMIOLOGY AND PATHOGENESIS
PFV appears sporadically in the vast majority of cases. One report exists of possible vertical transmission with both a mother and son affected, which suggests autosomal dominant inheritance. In two other reports, autosomal recessive inheritance was suggested; these included one case of fraternal twins, both of whom had PFV. 
Although no definite risk factors or confirmed systemic associations occur, maternal cocaine use during pregnancy of affected newborns has been reported.   Rarely, PFV occurs in conjunction with other ocular or systemic abnormalities, for example, microcephaly, mental retardation, spasticity, cleft palate, and short stature in the oculopalatocerebral dwarfism syndrome. One case of PFV associated with bilateral megalocornea and another with optic nerve coloboma have been noted. No sex predilection occurs.
The cause of PFV remains obscure. During ocular development, the primary vitreous fills the vitreous cavity as a fibrillar meshwork of mesenchymal tissue and serves as structural support for the hyaloid vasculature. The hyaloid vessels emerge
Figure 145-1 Hyaloid vasculature and primary vitreous during embryologic ocular development.
from the optic nerve and course anteriorly to nourish the developing lens and anterior segment structures ( Fig. 145-1 ). The hyaloid vessels and primary vitreous normally begin to involute in the second month of gestation, giving way to the secondary vitreous. If this regression does not occur completely, subsequent contraction and opacification of the primary vitreous along the hyaloid vascular system lead to the clinical presentation of PFV. This mechanism of maldevelopment has led to the term to describe this disease coined by Goldberg, persistent fetal vasculature syndrome. The specific insults that prevent regression of the primary vitreous remain unknown.
Failure of regression of the primary vitreous and hyaloid vasculature can result in a broad spectrum of findings. Pupillary strands and a Mittendorf’s dot represent the mildest manifestations and leukokoria with a dense retrolenticular membrane and/or retinal detachment the most severe. Depending on which intraocular structures are involved, the designation of anterior PFV, posterior PFV, or both can be assigned.
Anterior PFV consists of retrolenticular fibrovascular tissue that attaches to the ciliary processes and draws them centrally ( Fig. 145-2 ). Often, the elongated ciliary processes are visible readily through the dilated pupil. As the fibrous tissue contracts and remodels, cataract formation, shallowing of the anterior
Figure 145-2 Typical appearance of persistent fetal vasculature syndrome. An opacified retrolenticular fibrovascular membrane is attached to drawn-in ciliary processes.
chamber, and angle-closure glaucoma may develop. Iris vessel engorgement and recurrent intraocular hemorrhage can occur, which result in pain and possibly eventual phthisis bulbi. Microphthalmia is a prominent finding.
Posterior PFV consists of a prominent vitreous fibrovascular stalk that emanates from the optic nerve and courses anteriorly. Preretinal membranes at the base of the stalk are common. Tractional retinal folds and traction retinal detachment may be present. Retinal dysplasia and optic nerve hypoplasia have also been described. Various degrees of microphthalmia and leukokoria may occur in both anterior and posterior PFV.
DIAGNOSIS AND ANCILLARY TESTING
The diagnosis of PFV is frequently a clinical one. The young age at which affected patients are usually diagnosed means that an examination under anesthesia to confirm the diagnosis and to examine the fellow eye is often indicated. When the full constellation of clinical findings is present unilaterally, the diagnosis is usually straightforward. True cases of bilaterality have rarely arisen. It is in these cases of bilaterality, as well as in those that have atypical clinical presentations, that further history and ancillary testing may be beneficial. Positive family history, complicated birth history, and bilaterality, as seen in retinoblastoma, Norrie’s disease, and retinopathy of prematurity, are usually absent in PFV. Computed tomographic scanning can be used to evaluate the presence of intraocular calcification, which is seen frequently in retinoblastoma but not in PFV. Conversely, microphthalmia is a consistent feature of PFV but not most other causes of leukokoria. Bilateral axial length measurements with ultrasonography, therefore, are helpful. In addition, B-scan ultrasonography and computed tomographic scanning can be used to determine the extent of posterior segment involvement, namely retinal detachment, when not visible on examination.
The differential diagnosis of PFV is shown in Box 145-1 . The differential diagnosis of PFV includes the differential diagnosis of leukokoria. It is most important to exclude the diagnosis of retinoblastoma. Although retinoblastoma is usually seen in an average-size eye and PFV in a smaller eye, the diagnosis of retinoblastoma must be carefully ruled out. Bilaterality of leukokoria is also a possible point of confusion for retinoblastoma, Norrie’s disease, retinopathy of prematurity, and other
Figure 145-3 Persistent fetal vasculature. Abundant mesenchymal fibrovascular tissue can be seen just behind and within the posterior lens (L). Note the ends of the ruptured lens capsule (R). A persistent hyaloid vessel. (From Caudill JW, Streeten BW, Tso MO: Ophthalmology. 1985;92:1153.)
Differential Diagnosis of Persistent Fetal Vasculature Syndrome
Retinopathy of prematurity
Familial exudative vitreoretinopathy
causes of leukokoria. Coats’ disease and PFV tend to be unilateral, but bilateral PFV certainly does occur. Once the diagnosis of PFV has been established, therapeutic considerations can proceed.
The histopathology of PFV illustrates the preceding clinical findings ( Fig. 145-3 ). The primary vitreous is a plaque of numerous spindle cells in a collagen matrix. Fragile blood vessels are supplied by a patent hyaloid artery. The plaque is attached to drawn-in ciliary processes. Cataract formation may occur should a defect be present in the adjacent posterior capsule.
Controversy exists as to which patients should undergo surgery, especially because visual results are often poor and the fellow eye is usually normal. However, the natural course of severe anterior PFV typically culminates in angle-closure glaucoma and intraocular hemorrhage, seen most frequently in the first 3 years of life, often occurring suddenly. Consequently, many have advocated early surgical intervention to preserve the globe.  
When treatment for anterior PFV is considered, surgical intervention should be performed as soon as possible to shorten the duration of deprivational amblyopia. Reese originally described a two-stage procedure, which consisted of needling the lens and a later dissection of the retrolental membrane. With the advent of vitreous cutting instruments and fine intraocular forceps, a closed system, single-stage procedure has become the standard of care ( Fig. 145-4 ).     Posterior segment abnormalities can also be addressed with this instrumentation. The cataract and
Figure 145-4 Surgical management of persistent fetal vasculature syndrome (PFV). Vitreous cutting instruments are used to remove carefully lens and retrolenticular material. Anterior incisions at the limbus or pars plicata are often used to avoid the vitreous base and peripheral retina, which may be present anteriorly in PFV.
retrolental tissue can be reached by either a limbal or a pars plicata approach. The posterior approach is potentially hazardous if the peripheral retina is pulled up into the ciliary processes. Aggressive postoperative amblyopia therapy is critical. 
Surgery for severe isolated posterior PFV is rarely undertaken. Although the fibrovascular tissue can be dissected and the accompanying retinal detachment may reapproximate to the retinal pigment epithelium, visual outcomes are quite poor. This is a result of the associated retinal detachment, retinal dysplasia, and, most critically, the normal fellow eye causing dense amblyopia.
COURSE AND OUTCOME
Visual results after treatment for PFV are generally poor, with affected eyes frequently manifesting hand motion or light perception vision only. The early two-stage approaches rarely achieved vision of 20/400 (6/121) or better. With modern surgical techniques, outcomes of 20/40 (6/12) to 20/200 (6/60), although uncommon, are possible. Posterior segment involvement is a poor prognostic sign for ambulatory vision.    However, visual acuities of 20/60 (3/18) to 20/800 (6/266) in some eyes that have posterior PFV have been reported. This review again supported aggressive amblyopia therapy as being critical to successful visual outcomes but noted that final vision is limited eventually by the degree of maldevelopment.
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