Periventricular leukomalacia (PVL) is a disease characterized by ischemic injury to the white matter adjacent to the lateral ventricles of the brain. It is primarily caused by hypoxic-ischemic events during the third trimester of pregnancy or the perinatal period.
A characteristic ophthalmologic finding associated with PVL is pseudoglaucomatous optic nerve cupping, which carries a risk of being misdiagnosed as normal-tension glaucoma. With advances in perinatal care improving the survival rate of preterm infants, the prevalence of PVL is expected to increase further in the future.
PVL itself is a perinatal injury and does not newly develop in adulthood. However, some patients may not be diagnosed in childhood and first visit an ophthalmologist in adulthood due to decreased vision or visual field defects, leading to a diagnosis of PVL. For details, see the section on “Diagnosis and Examination Methods”.
The severity and extent of the ophthalmological clinical picture of PVL depend on the degree of brain damage.
The clinical picture varies depending on the site of PVL damage. The characteristics of findings according to the level of visual pathway damage are shown below.
Prechiasmal Lesion
Ipsilateral visual acuity loss and visual field defect: Corresponding to the side of the lesion.
Color vision abnormality: Accompanied by dyschromatopsia.
Relative afferent pupillary defect (RAPD): Appears on the ipsilateral side in unilateral or asymmetric cases.
Optic atrophy: Unilateral or bilateral.
Postchiasmal and Pregeniculate
Contralateral homonymous hemianopia: Due to optic tract lesion.
Contralateral RAPD: Characteristic finding of optic tract disorder.
Band-shaped (bow-tie) optic atrophy: Appears in the contralateral eye. Reflects damage to crossing fibers.
Post-geniculate lesion
Optic atrophy due to trans-synaptic degeneration: Usually not seen in adult-onset post-geniculate lesions, but in perinatal injuries such as PVL, secondary optic atrophy occurs via trans-synaptic degeneration.
Pseudo-glaucomatous cupping: Presents with a large, deep cup in a normal-sized optic disc.
A finding specific to adult PVL patients is the importance of differentiation from normal-tension glaucoma.
| Feature | Glaucoma | PVL |
|---|---|---|
| Optic cup | Vertical cup enlargement | Horizontal (band-shaped) cupping |
| Visual field defect | Nasal step defect is common | Inferior-dominant visual field defect |
PVL is characterized by bilateral visual field defects that respect the horizontal meridian and are inferior-dominant, whereas normal-tension glaucoma often shows nerve fiber layer-type defects such as arcuate scotomas and nasal step defects. The pattern of optic disc cupping also differs; PVL presents with horizontal (band-shaped) cupping.
PVL develops against the background of immaturity of the periventricular blood supply during the fetal period. Periventricular vascular development remains incomplete until late pregnancy, making this period vulnerable to adverse events.
The main risk factors are as follows.
When evaluating visual field defects or optic disc cupping in adult patients with a history of preterm birth, a detailed history of perinatal events is essential. The first step in suspecting and diagnosing PVL is obtaining the patient’s history.
Perform a complete neuro-ophthalmic examination.
This is an important test for differentiating pseudo-glaucomatous cupping from true glaucoma in PVL1).
| Feature | Glaucoma | Pseudo-glaucomatous PVL |
|---|---|---|
| RNFL thinning | Hourglass pattern (superior/inferior predominant) | Diffuse or nasal predominant |
| Papillomacular bundle | Preserved until end stage | May show thinning |
| Changes over time | Progressive | Non-progressive, stable |
Longitudinal OCT evaluation is particularly useful for differentiation; in PVL, the retinal nerve fiber layer thickness remains stable over the long term, which is a decisive difference from glaucoma.
Neuroimaging findings in PVL correspond to the timing and severity of the injury. In the early stage, periventricular white matter necrosis is observed, which may progress to intraparenchymal cyst formation in the subacute phase. In the late stage, parenchymal loss and ventricular enlargement occur. The topographic anatomical features of the injury typically correlate with the type and severity of visual field defects.
El Beltagi et al. (2022) reported a case of a 21-year-old man with optic nerve demyelination atrophy due to PVL that was misdiagnosed as normal-tension glaucoma for 5 years 1). Corrected visual acuity was 6/36 in the right eye and 6/12 in the left eye, with normal intraocular pressure of 14 mmHg. MRI confirmed reduced periventricular white matter volume and gliotic changes predominantly in the occipital lobe, leading to a diagnosis of PVL involving the optic radiation. After discontinuation of glaucoma treatment, no progression of visual field defects was observed during approximately 2 years of follow-up.
Trans-synaptic degeneration due to PVL causes a large cup and visual field defect in a normal-sized optic disc, and together with normal intraocular pressure, it closely resembles normal-tension glaucoma. Being young and having a stable course despite treatment are clues for differentiation. A detailed perinatal history is essential.
There is no fundamental treatment for visual impairment caused by PVL. Management is based on a comprehensive multidisciplinary approach.
Surgical intervention is usually not justified for the ocular findings of PVL. If strabismus is present, strabismus surgery may be performed during childhood.
The pathophysiology of PVL is understood in two stages: ischemic injury to the periventricular white matter, followed by transsynaptic degeneration.
The periventricular area of the fetal brain corresponds to a watershed region, and vascular supply remains immature until late gestation. When a hypoxic-ischemic event occurs during this period, the following cellular-level damage occurs.
These mechanisms lead to cell death and thinning of the periventricular white matter. PVL preferentially affects the deep periventricular white matter around the trigone, where active myelination is ongoing.
The optic radiation originates from the lateral geniculate body and runs adjacent to the lateral ventricle, making it susceptible to damage from PVL. Axonal disruption of the optic radiation causes transsynaptic degeneration, leading to retrograde atrophy of retinal ganglion cells beyond the lateral geniculate body.
The morphological changes in the optic nerve differ depending on the timing of the injury.
Because the lateral geniculate body is anatomically and functionally topographically organized, functional deficits in patients with PVL strongly depend on the site of injury. Involvement of extrastriate visual association areas can also cause impairments in object recognition, motion detection, and visual attention.
The significance of OCT in optic tract diseases is that measurement of the peripapillary retinal nerve fiber layer (cpRNFL) thickness indirectly evaluates all retinal ganglion cells, and measurement of the macular ganglion cell complex (GCC) enables earlier detection of damage. Reports have shown OCT abnormalities even in lesions posterior to the lateral geniculate body, supporting the concept of transsynaptic degeneration in PVL.
Transsynaptic degeneration is a phenomenon in which, when part of a neural circuit is damaged, upstream or downstream neurons connected via synapses also undergo secondary atrophy and degeneration. In PVL, damage to the optic radiation spreads retrogradely beyond the lateral geniculate body to retinal ganglion cells, causing optic atrophy.
The effectiveness of hypothermia therapy as a neuroprotective treatment for perinatal hypoxic-ischemic brain injury is being studied. Systemic cooling of newborns may suppress the progression of brain damage, but evidence specific to PVL is limited.
Diffusion imaging is expected to be a technique that can evaluate the relationship between structure and function in more detail, but further research is needed for clinical application.
