Persistent fetal vasculature (PFV), also known as persistent hyperplastic primary vitreous (PHPV), is a rare congenital anomaly that is caused by failure of regression of the primary vitreous and the embryonic hyaloid vascular system.1 As the term PHPV was most commonly used to refer to a condition of failure of regression of the components of the fetal vasculature that encase the posterior surface of the lens, Goldberg1 applied the term persistent fetal vasculature to this condition as it includes persistence of other components of the fetal intraocular vasculature. Goldberg1 coined this term as a more encompassing diagnosis that includes not only retrolental components, but also posterior components of the eye, including the zonular region, the vitreous, the retina, and the optic nerve.
PFV is frequently found in healthy full-term infants and more commonly occurs unilaterally, although it can occur bilaterally or in association with systemic syndromes.1,2 It can manifest with a combination of anterior and posterior segment abnormalities.1 Anterior segment findings include pupillary membranes, cataract, dragged ciliary processes, and retrolenticular opacity, and posterior segment findings include retinal dysplasia, vitreal stalk or membrane, and macular or optic nerve abnormalities.1–3 The spectrum of the ocular manifestations varies based on the degree of incomplete regression.1,3
We describe three cases of PFV with atypical findings with peripherally located remnants, one presenting with vitreous hemorrhage and another with a retinal tear secondary to retinal traction.
A 5-month-old healthy, white male was referred for evaluation of vitreous hemorrhage in the right eye noted on initial examination for congenital exotropia. He was born at 37 weeks gestational age. On ophthalmologic examination, the patient was aversive to light in both eyes. Anterior segment examination of both eyes showed clear corneas, anterior chambers were deep, and the lenses were clear. On dilated fundus examination, there was a limited view of the peripheral retina secondary to vitreous hemorrhage in the right eye, and the left eye was unremarkable. B-scan ultrasonography of the right eye demonstrated moderately dense vitreous opacities, including a large vitreous opacity in the midperiphery, without retinal detachment. Examination under anesthesia (EUA) confirmed the above findings. Intraocular pressure (IOP) was 18 mm Hg in the right eye and 14 mm Hg in the left eye. Dilated fundus examination demonstrated old vitreous hemorrhage covering the macula extending inferiorly in the right eye. Retinal vasculature appeared normal in both eyes except a stalk of tissue within the dense hemorrhage in the mid-periphery in the right eye. Fluorescein angiography (FA) showed abrupt termination of vasculature with abnormal dilation of end terminals without leakage in both eyes. The area under the hemorrhage was not well-visualized on FA, secondary to blockage; thus, it is unclear if there was perfusion of the stalk.
After discussion of the risk for amblyopia, the patient underwent 25-gauge pars plana vitrectomy. In the inferior midperiphery, under the densest portion of the hemorrhage, there was a vascular stalk within the vitreous (Figure 1). The vitreal stalk was cauterized. Postoperatively, the patient received patching therapy. At postoperative month 8, there was no recurrence of hemorrhage.
Fundus photograph of the right eye after pars plana vitrectomy in Case 1. Fundus photograph demonstrates vitreal stalk (white arrow) in the inferior midperiphery.
An 8-year-old healthy, white female was referred for a possible retinal tear in the right eye. The best-corrected visual acuity (BCVA) measured 20/30+ in both eyes, and spherical equivalent was −12.0 diopters (D) in the right eye and −14.0 D in the left eye. EUA revealed IOP of 20 mm Hg in the right eye and 19 mm Hg in the left eye. Anterior segment examination revealed a clear cornea, deep anterior chamber, and dilated iris in both eyes, with focal lens opacity superiorly in the right eye (Figure 2) and a clear lens in the left eye. Dilated fundus examination showed a myopic retina with a pink and flat optic nerve in both eyes, a persistent fetal vasculature stalk superotemporally with traction, and a retinal break at the base of the stalk in the right eye (Figure 2), and normal vasculature in the left eye. On FA, there was no filling of the stalk (Figure 2) and otherwise normal retinal vasculature in both eyes. Laser retinopexy of the retinal break was performed and included the area of retinal traction, encompassing the entire base of the stalk. At follow-up examination 5 months later, spectral-domain optical coherence tomography (SD-OCT) imaging of the right eye revealed an irregular foveal contour with incomplete foveolar development and an otherwise stable examination (Figure 3).
Fundus photographs, fluorescein angiogram (FA), and anterior segment photograph of the right eye in Case 2. Fundus photographs obtained during video indirect ophthalmoscopy demonstrating (A) superotemporal fibrovascular stalk with traction and a retinal break at the base of the stalk, (B) persistent fetal vasculature remnant at anterior aspect of fibrovascular stalk, and (C) scleral depression under area of insertion of peripheral stalk with traction and associated retinal changes. (D) Fundus photograph obtained with RetCam (Natus Medical, Pleasanton, CA) demonstrating superotemporal fibrovascular stalk. (E) FA demonstrating lack of perfusion of fibrovascular stalk in superotemporal periphery. (F) Anterior segment photograph shows posterior lenticular opacity in superotemporal periphery.
Fundus photograph and spectral-domain optical coherence tomography (SD-OCT) of the right eye after laser retinopexy in Case 2. (A) Fundus photograph demonstrating superotemporal laser retinopexy scars surrounding area of traction from persistent fetal vasculature stalk. SD-OCT demonstrating (B) elevation of retina with irregular anatomy within area surrounded by laser retinopexy and (C and D) irregular anatomy and contour of macula.
A 12-year-old healthy, white female was referred for a peripapillary choroidal neovascular membrane (CNVM) in the right eye. The BCVA measured 20/80 in the right eye and 20/40 in the left eye. Spherical equivalent was −15 D in the right eye and −13.0 D in the left eye. IOP measured 12 mm Hg in the right eye and 14 mm Hg in the left eye. Anterior segment examination revealed a clear cornea, deep anterior chamber, dilated iris, and clear lens in both eyes. Dilated fundus examination of the right eye showed a peripapillary lesion with surrounding peripapillary atrophy, nasal dragging of retinal vasculature, and a persistent fetal vasculature stalk in the nasal periphery (Figure 4). Fundus examination of the left eye showed nasal dragging of retinal vessels. FA demonstrated early hyperfluorescence with late staining at the base of the vitreal stalk consistent with a window defect (Figure 4). There was no filling of the stalk with fluorescein. Peripheral retinal vasculature showed late staining in both eyes. The peripapillary lesion demonstrated early hyperfluorescence with late leakage consistent with a CNVM. The patient underwent treatment for CNVM with three injections of intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) in the right eye.
Fundus photograph and fluorescein angiogram (FA) of the right eye in Case 3. (A) Widefield fundus photograph demonstrating a peripapillary lesion with surrounding peripapillary atrophy, nasal dragging of retinal vasculature, and a persistent fetal vasculature stalk in the nasal periphery (black arrow) and (B) late FA demonstrating late staining at the base of the vitreal stalk consistent with a window defect without filling of the stalk (yellow arrow).
During normal development, proliferating blood vessels of the fetal vasculature develop within the first month of gestation. The vascular network is maximally developed in 2 to 3 months and includes the following components: anterior tunica vasculosa lentis in the pupillary space, the anterior ciliary vessels to the iris and lens, the iridohyaloid vessels in the equatorial region of the lens that bridge the posterior tunica vasculosa lentis and the annular vessel, the posterior tunica vasculosa lentis, and the vasa hyaloidea propria.1,3 These vessels begin to regress during the fourth month and are largely absent at birth.1 Failure of regression of the primary vitreous and hyaloid system results in PFV.
Typical findings in posterior PFV include a retrolental fibrovascular stalk, retinal dysplasia, retinal folds or detachment, and optic nerve hypoplasia.2 Other conditions that also remain on the differential when evaluating a young patient with a peripheral posterior mass or stalk resembling PFV include ocular toxocariasis, medulloepithelioma, congenital retinal fold, retinoblastoma, or another Norrie disease protein-related retinopathy, such as familial exudative vitreoretinopathy.4–7 To our knowledge, these unique cases of PFV describe peripheral vitreal stalks without significant central or anterior involvement, which has not previously been described.
Visual outcome can vary with the spectrum of ocular manifestations, and as all of our patients had peripheral lesions, visual prognosis is favorable. One patient underwent vitrectomy with cauterization of the vitreal stalk for vitreous hemorrhage. Indirect laser retinopexy to an area of retinal traction peripherally to treat a retinal tear and prevent negative sequelae of traction was performed for the second case. Indications for surgical intervention for PFV have changed over the years as knowledge of the disease has increased and surgical techniques have advanced. The decision to perform surgery depends on a number of factors, such as the severity of disease, patient age, and visual prognosis. In patients with severe microphthalmia or advanced posterior PFV, the effectiveness of the surgery may be limited. Similarly, patients with mild clinical PFV findings without visual significance can be observed. If surgery is warranted, early intervention is recommended to decrease the period of deprivation amblyopia, as in our patient with vitreous hemorrhage.8 As the patient in Case 1 was 5 months old with visually significant vitreous hemorrhage, the decision was made to perform vitrectomy to clear the visual axis and cauterize the vitreal stalk to prevent recurrent hemorrhage. Additionally, as in previous studies that demonstrated useful vision after surgical treatment in conjunction with postoperative amblyopia therapy, our patient received patching therapy postoperatively.9,10
Although the vitreous hemorrhage in one of our patients may suggest possible perfusion of the remnant of fetal vasculature, the vitreal stalks did not fill completely with dye on FA in our patients. Some have reported fluorescein leakage from the persistent vessels, such as in a case of PFV in an adult by Gieser et al.11 Additionally, in another report of two eyes with persistent hyperplastic primary vitreous and hyaloid artery, there was filling of the remnants of the hyaloidal vascular system in both eyes.12
The persistent hyaloidal remnants in the more commonly described manifestations of PFV are the anterior and posterior tunica vasculosa lentis and the hyaloid artery. Another key component of the fetal vasculature is the vasa hyaloidea propria (VHP).9 In the mouse, the VHP consists of branching vessels from the hyaloid artery and has radiations in the vitreous on the internal surface of the retina.13 Additionally, capillaries from the VHP join the tunica vasculosa lentis at the equator of the lens.13 A whole branch of the VHP can regress, or small interconnections in the periphery can regress segmentally.13 Failure of regression of components of the VHP in animal models results in peripherally located membranes, which may be the cause for the vascular remnants in our patients.
These cases highlight the atypical nature and presentation of some cases of PFV. All patients had peripheral posterior PFV instead of the more commonly described combined (anterior and posterior) central PFV. Given the subtle posterior findings in patients with more peripheral PFV and the lack of symptoms in some patients, we suspect this PFV variant is underdiagnosed.
- Goldberg MF. Persistent fetal vasculature (PFV): An integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol. 1997;124(5):587–626. doi:10.1016/S0002-9394(14)70899-2 [CrossRef]
- Haddad R, Font RL, Reeser F. Persistent hyperplastic primary vitreous. A clinicopathologic study of 62 cases and review of the literature. Surv Ophthalmol. 1978;23(2):123–134. doi:10.1016/0039-6257(78)90091-7 [CrossRef]
- Silbert M, Gurwood AS. Persistent hyperplastic primary vitreous. Clin Eye Vis Care. 2000;12(3–4):131–137. doi:10.1016/S0953-4431(00)00054-0 [CrossRef]
- Liu Y, Zhang Q, Li J, Ji X, Xu Y, Zhao P. Clinical characteristics of pediatric patients with ocular toxocariasis in China. Ophthalmologica. 2016;235(2):97–105. doi:10.1159/000443215 [CrossRef]
- Cogan DG. Congenital anomalies of the retina. Birth Defects Orig Artic Ser. 1971;7(3):41–51.
- Nishina S, Suzuki Y, Yokoi T, Kobayashi Y, Noda E, Azuma N. Clinical features of congenital retinal folds. Am J Ophthalmol. 2012;153(1):81–87. doi:10.1016/j.ajo.2011.06.002 [CrossRef]
- Sims KB. NDP-related retinopathies. In: Adam MP, Ardinger HH, Pagon RA, , eds. GeneReviews. Seattle, WA; 1993.
- Walsh MK, Drenser KA, Capone A Jr, Trese MT. Early vitrectomy effective for bilateral combined anterior and posterior persistent fetal vasculature syndrome. Retina. 2010;30(4 Suppl):S2–8. doi:10.1097/IAE.0b013e3181d34a9e [CrossRef]
- Alexandrakis G, Scott IU, Flynn HW Jr, Murray TG, Feuer WJ. Visual acuity outcomes with and without surgery in patients with persistent fetal vasculature. Ophthalmology. 2000;107(6):1068–1072. doi:10.1016/S0161-6420(00)00100-7 [CrossRef]
- Mittra RA, Huynh LT, Ruttum MS, et al. Visual outcomes following lensectomy and vitrectomy for combined anterior and posterior persistent hyperplastic primary vitreous. Arch Ophthalmol. 1998;116(9):1190–1194. doi:10.1001/archopht.116.9.1190 [CrossRef]
- Gieser DK, Goldberg MF, Apple DJ, Hamming NA, Kottow MH. Persistent hyperplastic primary vitreous in an adult: Case report with fluorescein angiographic findings. J Pediatr Ophthalmol Strabismus. 1978;15(4):213–218.
- Menchini U, Pece A, Alberti M, Serini P, Brancato R. Hyperplastic primary vitreous with persistent hyaloid artery in 2 non-twin brothers. J Fr Ophtalmol. 1987;10(3):241–245.
- Ito M, Yoshioka M. Regression of the hyaloid vessels and pupillary membrane of the mouse. Anat Embryol. 1999;200(4):403–411. doi:10.1007/s004290050289 [CrossRef]