From the Department of Paediatric Ophthalmology and Strabismus (AK), Bombay City Eye Institute and Research Center, Mumbai; Department of Paediatric Ophthalmology and Strabismus (SS, PV), Aravind Eye Hospitals, Tamilnadu, India.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Anand Kumar, MS, DNB, Paediatric Ophthalmology & Strabismus Department, Bombay City Eye Institute and Research Centre, 5, Babulnath Road, Mumbai 400007, India.
Optic nerve hypoplasia is a nonprogressive congenital abnormality of one or both optic nerves presumably caused due to a failure of differentiation of the retinal ganglion cell layer between the 12- and 17-mm stages of embryonal development.1–3 It may be associated with numerous neruological disorders.3 Duane retraction syndrome has recently been included in the group of congenital cranial nerve dysinnervation disorders. In this condition, there is an abnormal connection between the nerve fibers meant to innervate the lateral rectus and medial rectus muscles. Both of these conditions can be caused by a disturbance of neuronal development during embryogenesis. To the best of our knowledge, this is the first case of bilateral Duane retraction syndrome associated with bilateral optic nerve hypoplasia.
An 8-year-old boy was seen in our pediatric out-patient department with complaints of squinting since birth. He was the product of a full-term pregnancy from a nonconsanguineous marriage. His antenatal, natal, and postnatal history was unremarkable. There was no family history of strabismus or other congenital anomalies. There was a history of right congenital talipes equinus varus correction performed at the age of 2 years. The patient was diagnosed by his pediatrician as having obesity with developmental delay.
On examination, the best-corrected visual acuity was 6/9 and 6/36 in the right eye and left eye, respectively. There was no significant refractive error. The patient had a chin depression with head tilt to the right side. The left eye showed congestion in the interpalpebral fissure temporally. Pupillary reactions in both eyes were normal and there was no afferent pupillary defect. Fundus examination revealed optic disc hypoplasia in both eyes with double ring sign (Fig. 1). The ratio of disc to macula/disc diameter on the fundus photograph was more than 4.5 in both eyes, which is characteristic of optic nerve hypoplasia.1 Ocular motility examination showed an esotropia of 85 prism diopters in the left eye for both near and distance. Abduction was restricted −4 (on a scale of 0 to 4) with upshoot on adduction and V pattern in both eyes. The abduction improved on elevation. On adduction, globe retraction was seen in the left eye more than the right eye (Fig. 2). There was no evidence of manifest or latent nystagmus.
Figure 1. Fundus Photograph of the Right Eye (A) and the Left Eye (B) Showing Small Discs with Circumpapillary Halo (double Ring Sign). Also Note the Ratio of Disc to Macula/disc Diameter in Both Eyes Is More than 4.5.
Figure 2. (A) On Attempted Right Gaze There Is Marked Limitation of Abduction in the Right Eye and Mild Globe Retraction in the Left Eye. (B) Clinical Photograph Showing Large Esotropia in the Left Eye in Primary Gaze. (C) On Attempted Left Gaze There Is Marked Limitation of Abduction in the Left Eye and Marked Globe Retraction in the Right Eye.
Systemic examination showed the boy to be obese (37 kg) and of short stature (124 cm). The right ankle joint showed a scar over its posterior aspect indicative of congenital talipes equinus varus correction surgery. An endocrinological evaluation of the child was found to be within normal limits.
Non-contrast computed tomography scan of the brain showed a small arachnoid cyst in the right medial and anterior temporal regions with minimal hypoplasia of the underlying temporal lobe. Thinning of both optic nerves, optic chiasms, and lateral geniculate bodies were seen. Mild dilatation and splaying of the body and posterior horns of lateral ventricles was seen. There was minimal preferential atrophy of bitemporal cortex with dilatation of sulci (Fig. 3). There was no evidence of absent corpus callosum, septum pellucidum, or ectopic posterior pituitary gland.
Figure 3. Computed Tomography Scan of the Brain. (A) Axial View Showing Marked Thinning of Optic Nerves in Both Eyes (thin Arrows). Note the Presence of an Arachnoid Cyst (bold Arrow Head) in the Right Medial and Anterior Temporal Regions with Minimal Hypoplasia of Underlying Temporal Lobe. (B) Coronal View Showing Transverse Section of Small Optic Nerves in Both Eyes (thin Arrows).
The patient was advised to patch the right eye 6 hours per day. At the end of 6 months, the visual acuity of the left eye improved to 6/18. It showed no improvement during the next 6 months despite good compliance with patching. The patient then underwent surgical correction for squint under general anesthesia. Forced ductions performed on the table were severely restricted to abduction in both eyes. We performed medial rectus recession in both eyes to 13 mm from the limbus, anticipating undercorrection. Lateral rectus resection was not performed because both eyes showed globe retraction on adduction. One month postoperatively, the patient had a residual esotropia of 25 prism diopters with a limited abduction of −3 in both eyes.
Once considered a rare anomaly, optic nerve hypoplasia is probably the most common congenital optic nerve anomaly encountered in pediatric ophthalmic practice. It is a non-progressive congenital abnormality of one or both optic nerves associated with a diminished number of axons in the involved nerve(s) with normal development of supporting tissues and the retinal vascular system.2 Histologically, the retinal nerve layer, the number of ganglion cells, and the optic nerve fibres are reduced.3
The cause of optic nerve hypoplasia was initially believed to be a failure of differentiation of the retinal ganglion cell layer from the inner neuroblastic layer between the 12- and 17-mm stages of embryonal development.2,4 However, this theory fails to explain the pathogenesis of the commonly associated midline brain defects. More recently, it has been postulated that the excessive axonal regression that occurs following the overdevelopment of retinal ganglion cells may be responsible for optic nerve hypoplasia.5
Numerous neurological conditions have been found to be associated with optic nerve hypoplasia.2 Twenty-seven percent of patients with optic nerve hypoplasia have associated partial or complete absence of septum pellucidum, a condition known as septo-optic dysplasia.6
Duane retraction syndrome is a congenital cranial dysinnervation disorder in which the nerve fibers meant for the medial rectus muscle innervate the lateral rectus muscle. It is usually a sporadic condition, and patients having the sporadic form are at 10 to 20 times greater risk of having other congenital malformations.7 Its frequent association with certain congenital malformations suggests a developmental disturbance between the fourth and tenth week of embryogenesis, an observation that is corroborated by studies of children with thalidomide embryopathy.8
There have been previous reports of Duane retraction syndrome with optic nerve hypoplasia.9,10 A 21-year-old woman with congenital heart disease, Klippel–Feil anomaly, Duane retraction syndrome, and optic nerve hypoplasia has been described in the literature.9 Denslow and Sims10 reported the case of a 4-year-old boy with unilateral Duane retraction syndrome and optic nerve hypoplasia. Aguirre-Aquino et al.11 described the case of a 4-year-old boy having unilateral Duane retraction syndrome with DeMorsier syndrome. Our patient probably had a more severe disturbance during embryogenesis resulting in underdevelopment of both sixth nerve nuclei presenting as bilateral Duane retraction syndrome, more severely affected anterior visual pathway development, arachnoid cyst, and atrophy of bitemporal cortex. However, it may be possible that the findings of dilated lateral ventricles and atrophied bitemporal cortex represent a mild form of coexisting periventricular leukomalacia.
This case corroborates the hypothesis that a disturbance in embryogenesis during the second gestational month could lead to Duane retraction syndrome. We postulate that the severity of the maldevelopment depends on the extent of the disturbance or the duration for which it acts on the developing fetal tissues. This disturbance may have resulted from a mutation in a developmental gene, exposure to a teratogenic agent, or a combination of factors. A milder noxious stimulus may cause isolated optic nerve hypoplasia, whereas a stronger stimulus may cause generalized disturbance of neuronal development including the entire anterior visual pathway, septum pellucidum, pituitary gland, and sixth nerve nuclei. Our case represents an intermediate form of neuronal disturbance between the two ends of this spectrum.
- Zeki SM, Dudgeon J, Dutton GN. Reappraisal of the ratio of disc to macula/disc diameter in optic nerve hypoplasia. Br J Ophthalmol. 1991;75:538–541. doi:10.1136/bjo.75.9.538 [CrossRef]
- Zeki SM, Dutton GN. Optic nerve hypoplasia in children. Br J Ophthalmol. 1990;74:300–304. doi:10.1136/bjo.74.5.300 [CrossRef]
- Hotchkiss ML, Green WR. Optic nerve aplasia and hypoplasia. J Pediatr Ophthalmol Strabismus. 1979;16:225–240.
- Scheie HC, Adler FH. Aplasia of the optic nerve. Arch Ophthalmol. 1941;26:61–70.
- Provis JM, van Driel D, Billson FA, Russel P. Human fetal optic nerve: overproduction and elimination of retinal axons during development. J Comp Neurol. 1985;238:92–100. doi:10.1002/cne.902380108 [CrossRef]
- Acers TE. Optic nerve hypoplasia: septo-optic-pituitary dysplasia syndrome. Trans Am Ophthalmol Soc. 1981;79:425–457.
- DeRespinis PA, Caputo AR, Wagner RS, Guo S. Duane’s retraction syndrome. Surv Ophthalmol. 1993;38:257–288. doi:10.1016/0039-6257(93)90077-K [CrossRef]
- Miller MT. Thalidomide embryopathy: a model for the study of congenital incomitant horizontal strabismus. Trans Am Ophthalmol Soc. 1991;89:623–674.
- Awan KJ. Association of ocular, cervical, and cardiac malformations. Ann Ophthalmol. 1977;9:1001–1011.
- Denslow GT, Sims M. Duane’s retraction syndrome associated with optic nerve hypoplasia. J Pediatr Ophthalmol Strabismus. 1980;17:26–28.
- Aguirre-Aquino BI, Rogers DG, Traboulsi EI. A patient with de Morsier and Duane syndromes. J AAPOS. 2000;4:243–245. doi:10.1067/mpa.2000.105303 [CrossRef]