Persistent fetal vasculature (PFV) is classically a unilateral sporadic condition defined by the presence of one or more components of the hyaloid vascular system persistent at birth.1,2 Despite traditional classifications subdividing this condition into purely anterior or posterior forms, PFV typically presents with a combination of both forms involving the iris, lens, and vitreous with patent or sclerosed fetal vascularity to these structures.1 Management depends on the extensiveness of the vascular tissue and related complications of hemorrhage, retinal traction, and glaucoma. Importantly, it should be recognized that PFV can occur in approximately 20% of eyes displaying medulloepithelioma; thus, evaluation for a solid tumor is critical.3 Furthermore, medulloepithelioma (a potentially malignant tumor) often demonstrates a retrolenticular vascularized membrane, resembling PFV.4
We report a case of a patient initially suspected to have ciliary body medulloepithelioma and later, upon referral, confirmed to have PFV. Fluorescein angiography, ultrasonography, and ultrasound biomicroscopy were instrumental in establishing the lack of tumor. Specifically, fluorescein angiography depicted the direction of flow from the Mittendorf dot to the periphery of the lens, consistent with PFV and opposite to the flow related to the retrolenticular vascularized membrane from medulloepithelioma.5
A 17-month-old girl developed esophoria in the right eye with leukocoria and was found to have a possible ciliary body medulloepithelioma. Previous ocular and medical history were unremarkable.
On referral, visual acuity was fix and follow bilaterally. Intraocular pressures were 18 mm Hg in the right eye and 15 mm Hg in the left eye. The left eye was normal. Axial length of the eyes with ultrasonography was 22.9 mm in the right eye and 21.4 mm in the left eye. The left eye was normal and findings were limited to the right eye.
On examination, the right eye demonstrated findings suggestive of PFV, including non-perfused persistent pupillary membrane and Mittendorf dot on the posterior lens, with a patent hyaloid artery from the optic disc to the dot and temporal postlenticular vascular tissue encased by iris pigment epithelium and looping back to the dot. There was no evidence of nuclear or cortical lens opacity, but a temporal lens coloboma without zonular support contributed to a thicker lens with an egg shape (Figure 1A).
(A) The right eye displayed persistent pupillary membrane emanating from the pupillary margin of the iris and a white Mittendorf dot on the posterior lens capsule. There is misplaced pigment epithelium on the posterior lens surface sparing the postlenticular tunica vasculosa lentis. A lens coloboma is present temporally but not clearly seen in this photograph. (B) Fluorescein angiography of the anterior segment illustrates a bright Mittendorf dot with partial perfusion of posterior tunica vasculosa lentis giving “brittle star” appearance. The flow is from the dot to the periphery. (C) The right fundus revealed normal retina with slight macular dragging temporally and a barely visible hyaloid artery. The Mittendorf dot is seen out of focus as a bright white spot. (D) Fluorescein angiogram of the right fundus demonstrates perfusion of the hyaloid artery up to the lens and into the posterior tunica vasculosa lentis (out of focus).
Fluorescein angiography confirmed a perfused hyaloid artery emanating from the optic disc to the Mittendorf dot and expanding into the partially perfused postlenticular “brittle star” of vessels, leading into three perfused vessels of the posterior tunica vasculosa lentis looping temporally toward the coloboma and back to the Mittendorf dot (Figures 1B–1D). There was no iris neovascularization nor perfusion of the anterior tunica vasculosa lentis. Ultrasound biomicroscopy revealed slight temporal prominence of the ciliary processes and no evidence of iris or ciliary body solid mass. Ophthalmoscopically, the optic disc and retinal vessels were normal, except for minor temporal dragging in the macular region (Figure 1C). There was no peripheral retinal non-perfusion, detachment, or folds. Observation was advised and amblyopia patching instituted. On follow-up 1 year later, the findings remained stable.
PFV is characteristically a unilateral condition in which the physiologic hyaloid vasculature fails to completely regress, resulting in the persistence of one or more of its components at birth.1,2 This is considered a sporadic entity, but there is some evidence suggesting a possible relationship or overlap with mutations in FZD4 and NDP, typically found with familial exudative vitreoretinopathy, as well as systemic disorders including trisomy 13, 15, and 18, Walker–Warburg syndrome, and incontinentia pigmenti.1,6,7
This condition was first called persistent hyperplastic primary vitreous by Reese in 1955.2 This terminology adequately depicted the retrolenticular changes but failed to mention other components of fetal vasculature. Classic findings include fibrovascular membrane involving the posterior surface of the lens, causing leukocoria, dragging of ciliary processes, persistence of the hyaloid artery, presence of vitreous membranes and retinal folds, and secondary glaucoma.1,2 In 1997, Goldberg suggested renaming this condition as PFV to emphasize the responsibility of the persistent hyaloid vascular system in the manifestations of this disorder.1 The fetal vascular system includes the anterior and posterior tunica vasculosa lentis, iridohyaloid vessels, hyaloid artery, and vasa hyaloidea propria. This new terminology encompassed a broader spectrum of clinical manifestations, including persistent pupillary membrane, iridohyaloid vessels, Mittendorf dot, vasa hyaloidea propria, hypoplasia or dysplasia of macula or optic nerve, congenital non-attachment of the retina, and alterations in size and shape of the globe.1
The numerous phenotypical characteristics of PFV can simulate other conditions, including Coat’s disease, familial exudative vitreoretinopathy, incontinentia pigmenti, Norrie disease, ocular toxo-cariasis, rhegmatogeneous retinal detachment, retinopathy of premature, and sickle cell retinopathy. Neoplastic conditions such as retinoblastoma and medulloepithelioma should also be considered in the differential diagnosis.3–6 In our case, the referral diagnosis was medulloepithelioma, but clinical evaluation and imaging confirmed PFV.
Medulloepithelioma represents a tumor of the non-pigmented ciliary epithelium, classified as benign or malignant. The tumor appears as a fleshy amelanotic mass but can remain hidden behind the iris in the ciliary body recesses.4,5,8,9 Additional features include iris neovascularization leading to neovascular glaucoma, lens notch, lens subluxation, cataract, and a retrolental neoplastic cyclitic membrane.4,8 This membrane can create confusion in the differentiation of PFV from medulloepithelioma because both conditions can show retrolenticular vascularization.9,10 Kaliki et al.4 found that the neoplastic membrane always emanates from the main tumor toward the lens on the anterior hyaloid surface in the retrolenticular space, opposite to PFV. In our case, the direction of retrolenticular vascular flow was key to establishing the correct diagnosis. With PFV, the flow is from the hyaloid artery to Mittendorf dot through the brittle star to the lens periphery (Figure 1). In medulloepithelioma, the flow is from the solid tumor in the ciliary body across the posterior lens surface in a haphazard fashion, opposite to PFV.5 Fortunately, in our case, there was no ciliary body mass on ultrasonography.
PFV is a unilateral sporadic condition that should be differentiated from ciliary body medulloepithelioma and other conditions. Despite some overlapping features, detailed clinical evaluation and imaging studies are advised to delineate the congenital malformation of PFV from the neoplastic medulloepithelioma.
- Goldberg M. 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;124:587–626. doi:10.1016/S0002-9394(14)70899-2 [CrossRef]
- Reese AB. Persistent hyperplastic primary vitreous: the Jackson memorial lecture. Trans Am Acad Ophthalmol Otolaryngol. 1955;59:271–286.
- Broughton WL, Zimmerman LE. A clinicopathologic study of 56 cases of intraocular medulloepitheliomas. Am J Ophthalmol. 1978;85:407–418. doi:10.1016/S0002-9394(14)77739-6 [CrossRef]
- Kaliki S, Shields CL, Eagle RC Jr, et al. Ciliary body medulloepithelioma: analysis of 41 cases. Ophthalmology. 2013;120:2552–2559. doi:10.1016/j.ophtha.2013.05.015 [CrossRef]
- Sharma P, Shields CL, Turaka K, Eagle RC Jr, Shields JA. Ciliary body medulloepithelioma with neoplastic cyclitic membrane imaging with fluorescein angiography and ultrasound biomicroscopy. Graefes Arch Clin Exp Ophthalmol. 2011;249:1259–1261. doi:10.1007/s00417-011-1688-7 [CrossRef]
- Pollard ZF. Persistent hyperplastic primary vitreous (PHPV): diagnosis, treatment and results. Trans Am Ophthalmol Soc. 1997;95:487–549.
- Shastry BS. Persistent hyperplastic primary vitreous: congenital malformation of the eye. Clin Experiment Ophthalmol. 2009;37:884–890. doi:10.1111/j.1442-9071.2009.02150.x [CrossRef]
- Shields JA, Eagle RC Jr, Shields CL, Potter PD. Congenital neoplasms of the non pigmented ciliary epithelium (medulloepithelioma). Ophthalmology. 1996;103:1998–2006. doi:10.1016/S0161-6420(96)30394-1 [CrossRef]
- Shields JA, Shields CL, Schwartz RL. Malignant teratoid medulloepithelioma of the ciliary body simulating persistent hyperplastic primary vitreous. Am J Ophthalmol. 1989;107:296–298. doi:10.1016/0002-9394(89)90318-8 [CrossRef]
- Shields JA, Shields CL. Tumors of the Nonpigmented Ciliary Epithelium. Intraocular Tumors: a Text and Atlas, 2nd ed. Philadelphia: Lippincott Williams and Wilkins; 2008:482–489.