Author Affiliations: Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago (Drs Hu, Chow, Kiernan, Blair, and Shapiro), Midwest Retina Consultants, SC, Park Ridge (Dr Garcia-Valenzuela), and Retina Consultants Ltd, Des Plaines (Drs Blair and Shapiro); and Department of Radiology, UC San Diego Medical Center, University of California, San Diego (Dr Mafee). Dr Kiernan is now with Ophthalmic Consultants of Long Island, Rockville Centre, New York.
Few entities exist in which optic nerve hypoplasia (ONH) is found in association with peripheral retinal nonperfusion. Among these are the congenital muscular dystrophies with abnormal glycosylation of α-dystroglycan, consisting of Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy, characterized by defective brain migration and ocular abnormalities. Posterior segment findings in these disorders have included ONH as well as retinal dysplasia.1 Herein, we describe a full-term girl not only with ONH and bilateral peripheral retinal nonperfusion with resultant tractional retinal detachments but also with severe brain abnormalities including lissencephaly and hydrocephalus.
A 3785-g girl born at 39 weeks' gestation was referred for bilateral retinal detachments. The prenatal course was uneventful, and there was no family history of eye or neurological abnormalities.
Shortly after birth, she developed seizures. Magnetic resonance imaging revealed massive dilatation of the lateral ventricles secondary to atrophy and hydrocephalus, marked cortical dysplasia and lissencephaly, periventricular calcifications, and a thin corpus callosum (Figure 1). Although the calcifications were suspicious for cytomegalovirus infection, serologic and urine culture results were negative. The serum creatine kinase level, to evaluate for a muscular dystrophy, was normal.
Figure 1. Coronal (A) and axial (B) T1-weighted magnetic resonance images demonstrate large dilatation of the lateral ventricles. The brain was not small but appeared smooth without gyri and sulci. The primary sylvian fissures were not seen, suggestive of developmental arrest (cortical dysplasia). A indicates anterior; P, posterior; and S, superior. C, Axial computed tomography shows dilated lateral ventricles along with paraventricular calcifications. There were small calcifications adjacent to the perimesencephalic cistern as well.
Examination revealed normal anterior segments. Fundus photography of the right eye showed a large tractional retinal detachment involving the macula, obscuring both the macula and the optic nerve, with posterior retinal vessels dragged and distorted into a retinal fold (Figure 2A). Fluorescein angiography demonstrated massive leakage off the stalk and along the apex of the horseshoe-shaped retinal detachment (Figure 2B). The optic nerve of the left eye showed a double ring sign consistent with ONH as well as foveal hypoplasia (Figure 2C). The retinal vessels terminated posteriorly, especially temporally with extraretinal fibrovascular proliferation extending into the vitreous and tractional detachment inferonasally and superotemporally (Figure 2D and E).
Figure 2. A montage Retcam color photograph (A) and a fluorescein angiogram (B) of the right eye show a large tractional retinal detachment involving the macula, obscuring both the macula and the optic nerve, with posterior retinal vessels dragged and distorted into a retinal fold. There was massive leakage off the stalk and along the apex of the horseshoe-shaped retinal detachment. C, A Retcam photograph of the left eye shows a double ring sign consistent with optic nerve hypoplasia. It also demonstrates an undifferentiated macular zone and foveal hypoplasia. A montage color photograph (D) and a fluorescein angiogram (E) of the left eye show the retinal vessels terminated posteriorly, especially temporally (arrowheads) (E) with extraretinal vascularization extending into the vitreous and tractional detachment inferonasally and superotemporally (arrows) (D). F, A montage color photograph of the left eye 3 months after laser treatment and pars plana vitrectomy shows a completely attached retina, peripheral laser scars, and an undifferentiated fovea.
Laser photocoagulation was applied to the avascular retinal zones. The patient subsequently underwent vitrectomy in both eyes. Three months later, the left retina was attached completely (Figure 2F) but the right retina remained detached.
There is a spectrum of disorders with ocular and neurological manifestations that overlap those of our patient. In the congenital muscular dystrophies, an underlying defect in glycosylation is thought to result in severe defects in neuronal migration, thus causing hypoplasia of various brain and eye structures.2 Walker-Warburg syndrome is the most severe, with brain abnormalities including lissencephaly, hydrocephalus, cerebellar malformation, hypomyelination of the white matter, and agenesis of the corpus callosum.3 Ocular posterior segment abnormalities include retinal dysplasia as well as hypoplasia or atrophy of the optic nerve and macula. Lissencephaly can also be found in Fukuyama congenital muscular dystrophy and muscle-eye-brain disease with associated ONH and retinal hypoplasia.4 A case of genetically proven muscle-eye-brain disease with ONH and peripheral retinal nonperfusion with secondary fibrovascular proliferation and retinal detachment was recently described.2 Our patient shares many similar features but had no evidence of a muscular dystrophy, with clinically absent hypotonia and a normal creatine kinase level. Additionally, a case of de Morsier syndrome with similar ocular findings of bilateral peripheral retinal nonperfusion and neovascularization with resultant retinal detachment was reported recently.5 We suggest that the abnormal neuronal development that led to lissencephaly resulted in optic nerve and retinal maldevelopment and subsequent associated retinal vascular maldevelopment. Tractional retinal detachment is an end stage of a process that starts with nonperfusion and progresses to ischemia and extraretinal fibrovascular proliferation in a variety of pediatric retinal diseases.
Although the cause of neural maldevelopment in our patient remains elusive, her case supports the idea that patients with severe neuronal migration deficits should be evaluated for ONH and abnormal retinal vasculature development, even without evidence of a muscular dystrophy.
Correspondence: Dr Shapiro, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, 1855 W Taylor St, Chicago, IL 60612 (email@example.com).
Author Contributions: Dr Shapiro had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Financial Disclosure: None reported.
Thank you for submitting a comment on this article. It will be reviewed by JAMA Ophthalmology editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 1
Customize your page view by dragging & repositioning the boxes below.
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.