Optic Nerve Developmental Disorders and Neuroimaging Techniques

Optic nerve developmental disorders encompass a spectrum of congenital and early‐onset conditions characterised by underdevelopment, malformation or absence of the optic nerve. Chief among these are optic nerve hypoplasia (ONH), characterised by a reduced calibre of the optic nerve and associated retinal ganglion cell loss, and septo-optic dysplasia (SOD), in which ONH coincides with midline brain anomalies and pituitary dysfunction. Clinical manifestations range from mild visual impairment to profound blindness, often accompanied by endocrine and neurodevelopmental sequelae. Over the past decade, high-resolution structural and functional neuroimaging techniques have transformed diagnosis and prognostication. Spectral-domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA) provide in vivo quantification of retinal layer thickness and microvascular networks, while advanced magnetic resonance imaging (MRI) modalities, including diffusion tensor imaging (DTI), elucidate axonal integrity and brain-stem connectivity. Integrating multimodal imaging with functional assessments, such as electroretinography, has improved our understanding of structure–function relations, guided management and highlighted subclinical involvement of fellow eyes in unilateral presentations.

Research from Nature Portfolio

Recent studies employing SD-OCT and OCTA have delineated sectoral patterns of peripapillary retinal nerve fibre layer (pRNFL) thinning and microvascular alterations in ONH. High-resolution analyses reveal that pRNFL thickness is markedly reduced across all sectors in affected eyes, correlating strongly with visual acuity. OCTA further uncovers regional increases in superficial and deep capillary densities, suggestive of compensatory remodelling, alongside focal reductions in radial peripapillary capillary flow. These microvascular findings enhance the structural assessment and may serve as biomarkers for visual prognosis.

Complementary investigations have combined SD-OCT with full-field and focal electroretinography to assess retinal function in ONH. These reveal prominent thinning of the ganglion cell complex nasally and temporally, concurrent with preserved outer retinal layer thickness in many patients. Electrophysiological recordings demonstrate reduced photopic negative responses and focal macular deficits, while peripheral function remains largely intact. This integration of imaging and functional data underscores the selective vulnerability of retinal ganglion cells and offers a refined framework for monitoring disease progression.

Optic Nerve Developmental Disorders and Neuroimaging Techniques publication trend

The graph below shows the total number of articles in optic nerve developmental disorders and neuroimaging techniques across all publications each year (not limited to Nature Index journals).

Technical terms

Optic nerve hypoplasia: A congenital condition in which the optic nerve is abnormally small owing to reduced retinal ganglion cells and axons.

Septo-optic dysplasia: A syndrome combining optic nerve hypoplasia with midline brain anomalies (e.g., agenesis of the septum pellucidum) and pituitary hormone deficiencies.

Spectral-domain optical coherence tomography (SD-OCT): A non-invasive imaging modality that uses light waves to obtain high-resolution cross-sectional images of retinal layers and optic nerve head structures.

Optical coherence tomography angiography (OCTA): An extension of OCT that visualises blood flow in retinal and choroidal microvasculature without dye injection.

Peripapillary retinal nerve fibre layer (pRNFL): The layer of axons immediately surrounding the optic disc, whose thickness reflects the integrity of retinal ganglion cell projections.

References

1. Optical coherence tomography and optical coherence tomography angiography findings in optic nerve hypoplasia and their relationships with visual acuity. Scientific Reports (2024).
2. Retinal Structure and Function in Eyes with Optic Nerve Hypoplasia. Scientific Reports (2017).
3. Neurodevelopmental impairments in children with septo-optic dysplasia spectrum conditions: a systematic review. Molecular Autism (2023).
4. Characteristic deviations of the optic disc and macula in optic nerve hypoplasia based on OCT. Acta Ophthalmologica (2024).
5. Whole genome sequencing unveils genetic heterogeneity in optic nerve hypoplasia. PLOS ONE (2020).