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Keywords:

  • optic chiasm;
  • achiasmia;
  • non-decussating retinal–fugal fibre syndrome;
  • congenital nystagmus;
  • optic nerve hypoplasia

Abstract.

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References

An 18-month-old white boy, observed by his parents at 1–2 months age to have poor visual attentiveness and nystagmus, underwent an ophthalmological evaluation. The patient also underwent unsedated 5-channel flash visual evoked potentials (VEP) and sedated electroretinogram (ERG) testing as well as magnetic resonance imaging (MRI) of the brain and orbits. The VEP in response to monocular stimulation demonstrated occipital asymmetry and was clearly suggestive of crossed asymmetry and also showed right optic nerve hypoplasia. The MRI and fundoscopic examinations supported the findings of achiasmia and probable optic nerve hypoplasia. The patient also had decreased Teller card visual acuity, nystagmus and a variable right esotropia. Neurological examination was normal. The ophthalmological and MRI findings in this 18-month-old male patient support the diagnosis of isolated non-decussating retinal–fugal fibre syndrome as well as hypoplasia of the optic nerve.


Introduction

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References

In primates with normal binocular vision, nasal retinal axons cross at the optic chiasm while temporal retinal axons extend ipsilaterally, projecting toward the lateral geniculate bodies and then to primary subcortical and cortical synapses, thus maintaining strict visuotopic segregation of the visual field. The two major conditions of aberrant optic projections, albinism and achiasmia (non-decussating retinal–fugal fibre syndrome), represent extreme abnormalities of primate visual organization. In albinism, ipsilaterally destined temporal retinal fibres erroneously decussate and project contralaterally at the optic chiasm. In the achiasmatic syndrome, nasal retinal fibres fail to decussate adequately at the chiasm, projecting instead ipsilaterally towards the lateral geniculate nuclei together with temporal retinal fibres (Apkarian 1996). In both these conditions, the corresponding visual field is consequently represented in complete (achiasmatic) or partial (albinism) mirror reversal in the laminae of the lateral geniculate nuclei (Williams et al. 1994). The reversed field is presumably re-interpreted normally by higher cortical processing such that the affected individuals are still able to visualize the world around them in a normal manner.

Since the historical mention of achiasmia in humans by the 16th century physician Andreas Vesalius, a small number of people with this rare condition have been reported in the literature. Using visual evoked potential (VEP) technology already in place for detecting albinism, Apkarian et al. (1993, 1995) first reported a case of non-decussating retinal–fugal fibre syndrome (achiasmia) in a female patient presenting with visual loss and nystagmus. Subsequently, in two other female patients presenting with reduced distance visual acuity (VA) for age, alternating esotropia, torticollis, head tremor and oculomotor instability, the same authors showed that the absence of recordable VEP responses from the occiput contralateral to the eye being stimulated was consistent with a paucity or complete absence of contralaterally directed nasal retinal−fugal fibres (Apkarian et al. 1993, 1994). The VEP results obtained in these studies were confirmed by magnetic resonance imaging (MRI) (which also ruled out other structural abnormalities). In the case of one of these patients, functional MRI also showed that for monocularly presented simple visual stimuli, only the ipsilateral striate cortex was activated (Victor et al. 2000). Follow-up studies to better characterize the nature of oculomotor misalignments and instabilities in these patients demonstrated classic congenital nystagmus in the horizontal planes, together with see-saw nystagmus in the vertical planes (Apkarian & Bour 2001). Horizontal oculomotor instabilities showed interocular yoking of both fast and slow phases, while vertical instabilities showed yoking primarily on fast phase. Alternating esotropia and vertical tropias were also documented. A similar case of isolated congenital achiasmia was documented in another 15-year-old girl, but in her case there was only a predominantly horizontal nystagmus, without evidence of a see-saw component (Jansonius et al. 2001). See-saw nystagmus was observed in a separate case report involving a 4-month-old female infant with achiasmia, but this patient also had associated brain abnormalities including midline craniofacial cleft lip and nasoethmoidal encephalocele (Leitch et al. 1996). Interestingly in this case, there was no horizontal nystagmus or strabismus. Among the unique features of the congenital non-decussating retinal–fugal fibre syndrome is the fact that the corresponding bi-temporal hemianopsia, which would be expected in an acquired optic chiasm tumour, or in trauma-induced split-chiasm cases, is not observed (Scott et al. 1997). Similarly, bi-nasal hemianopsia related to an absence of ipsilateral temporal retinal projections is not observed in human albinos.

Case report

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References

The patient, a white boy, the product of a full-term, first pregnancy, was born with a birth weight of 3.66 kg. There was no noteworthy difficulty in the patient's newborn nursery course, nor in his subsequent state of health. His parents first began to have concerns regarding his vision when he was 1–2 months of age. He was poorly visually attentive at this time and had nystagmus. When examined clinically at 4 months of age, he was noted to have poor vision with sluggish pupils, optokinetic nystagmus in all directions, intermittent downbeat nystagmus, and a roving pendular horizontal nystagmus. The optic nerves were thought to be slightly small by fundoscopy. The impression at that time was delayed visual maturation with possible optic nerve hypoplasia.

Magnetic resonance imaging of the brain was performed at 4 and 22 months of age. High-resolution sagittal, axial and coronal sequences were obtained through the orbits and chiasm.

The radiological findings (Fig. 1) were remarkable for the small appearance of the intraorbital portions of both optic nerves. The prechiasmic (intracranial) portion of the optic nerves was substantially hypoplastic on each side. The optic chiasm could not be confidently identified, indicating that it was either markedly hypoplastic or absent (Figs 2 and 3). The post-chiasmic optic radiations were hypoplastic as well. The pituitary gland was normal in appearance. The hypothalamus, septum pellucidum and corpus callosum were also normal. The brain ventricles were normal in size and position.

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Figure 1. Cranial MRI axial T2 weighted section through the orbits at the level of the optic nerves demonstrating bilateral optic nerve hypoplasia (arrowheads).

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Figure 2. Cranial MRI mid-sagittal T2 weighted section at the level of the chiasm and sella. The optic chiasm is absent at its expected location (curved arrow).

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Figure 3. Cranial MRI coronal T2 weighted section at the level of the sella. No optic chiasm is present (arrow).

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At 19 months of age, the subject continued to be in general good health. He was below the average curve for height and weight, while his head circumference was in the 75–90th percentile. His speech was normal for his age, with a vocabulary of between three and six words. A review of systems was otherwise non-contributory.

On ophthalmic examination at 19 months of age, the patient did not respond to any of the Teller acuity targets with the right eye. His Teller acuity was 20/130 with the left eye. He strongly objected to patching the left eye at the time of the visit. Pupils were equal in size and briskly reactive to light and accommodation. A right afferent pupillary defect was present. Ductions and versions appeared grossly full. He had full abduction bilaterally by doll's reflex manoeuvres. By Krimsky reflex testing, he appeared to have a right esotropia of 18–20 Δ that was variable. He did not have see-saw nystagmus; rather he appeared to have random movements of his eyes. In some ways, these movements appeared to be similar to those in opsoclonus; however, his eyes did not return to primary position before making a saccade to another direction. He appeared to have right inferior oblique over-action. Cycloplegic refraction was − 0.75 sphere OD and + 0.75 + 0.50 × 090 OS. The orbits were normal to retropulsion. No ptosis was present. The anterior segment was grossly normal by inspection. He grossly attended to objects in all four quadrants of his visual fields. On dilated fundus examination, no hypoplasia of the optic nerves was appreciated; however, the view of the optic nerves was brief and challenging to assess. Throughout the examination and during interludes of portions of the examination the patient would walk around and play with toys. He did not bump into objects around him.

The patient underwent an unsedated flash VEP test at 19 months of age. The VEP was recorded from five occipital electrodes over O1 to O4 and Oz positioned in accordance with the International 10/20 system (Brigell 2001). Bright, white flashes (approximately 2.5 cds/m2), presented at a rate of 1.9 Hz, were used as stimuli. The amplifier bandpass filter was set to 1–100 Hz and 80–100 responses were averaged each run. Monocular stimulation showed occipital asymmetry of the responses when the left eye was stimulated (Fig. 4A). A negative peak was observed at approximately 90 ms over the ipsilateral hemisphere, whereas a positive response with the same latency was seen over the contralateral hemisphere. Stimulation of the right eye produced abnormal responses with small amplitudes and long latencies over both hemispheres. Subtraction of the responses obtained over O3 from O4 gave tracings suggestive of a crossed asymmetry (Fig. 4B).

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Figure 4. (A) The flash VEPs driven from the right eye (left column) have a profoundly abnormal appearance, whereas the responses obtained when the left eye (right column) was stimulated reveal occipital asymmetry. The electrode positions, from the leftmost (O3) to the rightmost position (O4), are indicated between the columns. Oz is in the midline between the left and right visual cortices. The arrowed responses show the reversal of polarity when responses from the left (O3) and right (O4) hemispheres are compared. (B) The responses from O3 are subtracted from O4. The arrow shows one part of the tracings that shows crossed asymmetry. Horizontal calibration 100 ms; vertical 7.5 µV for both A and B.

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An MRI scan of the brain and orbits was repeated at 22 months of age. Marked hypoplasia of the intraorbital and prechiasmatic portion of the optic nerves and postchiasmatic optic tracts was noted. The optic chiasm was not identifiable. The pituitary gland and stalk were normal. The cerebral ventricles and sulci were normal. No focal area of abnormal brain signal was present.

At 23 months of age, a sedated, full-field flash ERG in accordance with ISCEV (International Society for Clinical Electrophysiology of Vision) protocol (Marmor et al. 2004) was performed, which showed normal responses in both eyes.

Discussion

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References

In albino subjects, following full-field left eye stimulation, the peak of the potential distribution lateralizes to the contralateral right occiput, whereas following right eye stimulation, the response lateralizes to the contralateral left occiput. In achiasmats, a peak response on full-field single eye stimulation would be observed over the ipsilateral occiput. The result of the VEP of the left eye in our patient was consistent with an achiasmic or non-decussating retinal–fugal fibre syndrome, with no crossing of fibres to the opposite hemispheres and only ipsilateral occipital responses to ocular stimulation (Apkarian et al. 1993, 1995; Dutton 1994; Thompson et al. 1999). With appropriate age-dependent misrouting protocols the electrophysiological testing is considered remarkably sensitive and specific for detecting albinism and achiasmia (Leitch et al. 1996). However, the lack of a normal response with stimulation of the right eye is unusual for achiasmia alone. Given the normal flash ERG obtained from this eye, the most likely explanation to the profoundly abnormal VEP was an additional underlying dysfunction or hypoplasia of the right optic nerve. This was supported as well on examination, by detection of a right relative afferent pupillary defect. The patient's roving eye movements were consistent with other descriptions of abnormal ocular motility in documented cases of achiasmia. The ability of the patient to otherwise interact normally with his environment was further testimony that visual field processing at higher cortical levels was compensating for the absence of chiasmal decussation.

The uniqueness of the non-decussating retinal–fugal fibre syndrome as described by Apkarian et al. (1993, 1995) and by ourselves in the above report, lies in the fact that absence of the optic chiasm can occur as an isolated embryological anomaly and need not be associated with other central nervous system defects, endocrinological dysfunction, or congenital malformations. Our patient was otherwise attaining normal developmental milestones. An extensive review of the literature found only one other case of isolated bilateral aplasia of the optic nerves, chiasm and tracts in an otherwise healthy 2-month-old female infant (Scott et al. 1997). The isolated findings in our patient underscored the important distinction between classic congenital achiasmia and many other cases of structural and functional achiasmia with associated developmental anomalies like midline craniofacial clefting (Leitch et al. 1996), or achiasmia secondarily induced from tumour growth (Dutton 1994) or trauma. In a study designed to demonstrate that chiasmal hypoplasia or total achiasmia need not be an isolated developmental anomaly, Thompson et al. (1999) gathered and clinically analysed data from five young patients who each demonstrated a different degree of afferent fibre paucity at the optic chiasm by VEP and MRI testing. They showed that in all their patients variable degrees of achiasmia were associated with findings as diverse as cleft lip and palate, mild holoprosencephaly, septo-optic dysplasia (DeMorsier's syndrome), panhypopituitarism and cognitive delay. These patients also had a wide variety of optic disc appearances ranging from normal to frankly hypoplastic and colobomatous. Thompson et al. (1999) speculated further that the spectrum of structural phenotypes associated with achiasmia suggested a possible underlying role for the PAX family of developmental control genes which code for transcription factors with dynamic and restricted expression patterns directly affecting cell differentiation and regionalization in the neuroprimordium. Murine studies in Pax2 mutant mice demonstrate a gap in the optic recess through which first retinal axons normally migrate is absent, resulting in an inability for these neurons to form the optic chiasm. In this mutant mouse model, no retinal axons cross the midline; all of them enter the ipsilateral optic tract (Torres et al. 1996).

In effect, the interesting and unique neuro-ophthalmological findings reported in our patient are consistent with several other rare cases of non-decussating retinal–fugal fibre syndrome and justify attentive follow-up to maximize his full visual potential. In the light of recent advances in the domains of cellular and molecular biology, the underlying defect in this patient is likely to represent failure in signalling and cell differentiation pathways involved in central nervous system development during the first trimester of gestation.

Acknowledgement

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References

This study was supported in part by an unrestricted grant from the Research to Prevent Blindness, Inc., New York, to the Department of Ophthalmology at the University of Minnesota Medical School.

References

  1. Top of page
  2. Abstract.
  3. Introduction
  4. Case report
  5. Discussion
  6. Acknowledgement
  7. References
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