The Challenge of Diagnosing a Rare Hereditary Disorder in a Young Patient

Feb 21, 2020 2:00 PM


Combination of Imaging Procedures Provides Insight in FEVR Case

Figure 1. A fundus photograph of the right eye shows peripheral avascular retina. The optic nerve was normal in color but appears pale due to camera flash in this photo.
Figure 1. A fundus photograph of the right eye shows peripheral avascular retina. The optic nerve was normal in color but appears pale due to camera flash in this photo.
Figure 1. A fundus photograph of the left eye demonstrates a stalk of retinal tissue from the pallid optic nerve to the anterior retina. The peripheral retina was avascular, noted during fluorescein angiography (FA).
Figure 1. A fundus photograph of the left eye demonstrates a stalk of retinal tissue from the pallid optic nerve to the anterior retina. The peripheral retina was avascular, noted during fluorescein angiography (FA).

By Srav Vegunta, MD; and Mary Elizabeth Hartnett, MD

A one-year-old girl was referred to the pediatric retina clinic by her pediatric ophthalmologist for evaluation of likely persistent fetal vasculature syndrome (PFVS), formerly known as persistent hyperplastic primary vitreous. She was born full-term with normal intrauterine development but had congenital motor nystagmus and amblyopia of the left eye, myopia of both eyes, and bilateral sensorineural hearing loss. There was no family history of eye or hearing problems. In the clinic, she had normal external appearance of the eyes and was able to fix and follow. Her glasses prescription was -4.25 +1.50 x 090 in the right eye and -4.75 sphere in the left eye. There appeared to be a retinal stalk emanating from the optic disc in her left eye, and the right retina grossly appeared normal. The examination was limited due to poor cooperation and a blonde fundus in both eyes. An exam under anesthesia was performed.

The patient had a normal anterior segment in the right eye. The left eye had a temporal and inferior retrolental membrane abutting the posterior lens capsule from a stalk of fibrovascular and retinal tissue extending from the optic nerve (Figure 1).

Figure 2. FA of the right eye late phase demonstrates peripheral avascular retina, seen to the left of the image.
Figure 2. FA of the right eye late phase demonstrates peripheral avascular retina, seen to the left of the image.
Figure 2. Another FA of the right eye late phase also demonstrates peripheral leakage from a temporal vascular frond.
Figure 2. Another FA of the right eye late phase also demonstrates peripheral leakage from a temporal vascular frond.

The retina of the right eye had peripheral avascularity and whitish tissue at the junction between the
vascular and avascular retina (Figure 2).

Imaging was performed on both eyes. Optical coherence tomography (OCT) demonstrated retained inner layers of the retina at the fovea of the right eye and no obvious fovea of the left eye (Figure 3). A fluorescein angiogram (FA) demonstrated peripheral avascular retina in the right eye with leakage from temporal neovascularization. Evidence of retinal vessels was seen in the stalk of the left eye.

 

Diagnosis: Familial Exudative Vitreoretinopathy

Figure 3. Optical coherence tomography (OCT) of the right eye demonstrates retained inner layers of the retina at the fovea.
Figure 3. Optical coherence tomography (OCT) of the right eye demonstrates retained inner layers of the retina at the fovea.
OCT during an exam under anesthesia of the left eye demonstrates no fovea. It is possible the foveal was incorporated into the stalk.
OCT during an exam under anesthesia of the left eye demonstrates no fovea. It is possible the foveal was incorporated into the stalk.

The examination under anesthesia and imaging provided insight into the diagnosis and management for both eyes. First, eyes appeared about the same size, whereas in PFVS one eye can be smaller, but not always. Also, PFVS often presents with an inferonasal location in relationship to the lens capsule, whereas in our patient, the location was inferotemporal. The peripheral avascular retina in the right eye was bilateral, so the diagnosis was changed from PFVS to familial exudative vitreoretinopathy (FEVR). Because of leakage in the right eye, laser was performed to the peripheral avascular retinal area to reduce the risk of tractional retinal detachment that can occur with FEVR. Because of the evidence that the retina was pulled into the stalk abutting the posterior lens capsule in the left eye, no surgical intervention was recommended. Surgery carries the risk of causing a retinal break, with limited prognosis for macular reattachment or vision. Although FEVR can be associated with nystagmus, a future evaluation for albinism will be considered for our patient given her nystagmus, foveal hypoplasia, and blonde fundus.

Discussion

FEVR was first described in 1969 by Criswick and Schepens as an inherited condition of wide variability. The condition may be associated with exudation and retinal detachment or intravitreal neovascularization and tractional retinal detachments. The presentation classically has been described as one of bilateral incomplete vascularization of the peripheral retina in an infant that was born full term. However, even within the same individual there can be variability in phenotype, including in our patient in whom there was a stalk of tissue. This exam finding led to the initial diagnosis of a unilateral process, PFVS. It is important to consider FEVR when a patient appears with seemingly unilateral PFVS. FEVR can also have a “normal” fellow eye, but more often a fluorescein angiogram can detect peripheral avascular retina. The prevalence and incidence of FEVR are unknown, but genetic variants can be detected in about 50 percent of patients, some in the Wnt signaling pathway (FZD4, LRP5, NDP, TSPAN12) as well as ZNF408, KIF11, and CTNNB1. Genetic counseling is helpful, as some FEVR genotypes have associated systemic findings, including osteoporosis with LRP5 variants.

About the Authors

Dr. Hartnett specializes in pediatric and adult retinal diseases and surgery and is founder and director of Moran’s Pediatric Retina Center, as well as PI of a laboratory focused on conditions including retinopathy of prematurity.

Dr. Vegunta is a third-year resident at the Moran Eye Center.

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