Autoimmune Microangiopathy in Neuro-Ophthalmic Disorders

Autoimmune microangiopathy encompasses disorders in which immune-mediated injury to the endothelium of small blood vessels produces clinical manifestations in both the central nervous system and visual pathways. The prototypical example, Susac syndrome, is characterised by a clinical triad of encephalopathy, branch retinal artery occlusions and sensorineural hearing loss. Pathophysiological studies reveal a combination of humoral factors, including anti-endothelial cell antibodies, and cytotoxic T-cell–mediated damage resulting in focal microvascular occlusion, blood–brain-barrier disruption and tissue ischaemia. Beyond Susac syndrome, similar processes can occur in systemic lupus erythematosus, antiphospholipid syndrome and other small-vessel vasculitides, where immune complexes and autoreactive lymphocytes target precapillary arterioles in the retina, optic nerve head and cerebral white matter. Clinically, these syndromes may present with acute visual field defects, rapidly progressive optic neuropathy or multifocal neurological symptoms. Early recognition relies on multimodal imaging—magnetic resonance techniques, fluorescein angiography and optical coherence tomography—combined with cerebrospinal-fluid analysis. Aggressive immunosuppression, tailored to disease severity, aims to abrogate endothelial injury, preserve microvascular flow and prevent irreversible neurological and visual sequelae.

Research from Nature Portfolio

Recent studies have elucidated a central role for CD8+ T-cell–mediated endotheliopathy in Susac syndrome. Analysis of patient samples and a transgenic mouse model demonstrated that activated cytotoxic CD8+ lymphocytes adhere to CNS microvessels, polarise granzyme B towards endothelial cells and induce microhaemorrhages. Therapeutic experiments showed that blocking T-cell adhesion via anti-α4 integrin markedly reduced vascular injury in the preclinical model, while off-label use of natalizumab in a small patient series coincided with clinical improvement. These findings position CD8+ T-cell infiltration and granzyme B release as actionable targets and support exploration of integrin-blocking strategies in refractory cases.

Autoimmune Microangiopathy in Neuro-Ophthalmic Disorders publication trend

The graph below shows the total number of articles in autoimmune microangiopathy in neuro-ophthalmic disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Autoimmune microangiopathy: Immune-driven inflammation and occlusion of small blood vessels.

Endotheliopathy: Pathological injury to the endothelial lining of blood vessels.

Branch retinal artery occlusion (BRAO): Focal blockage of a small retinal arteriole, causing visual field deficit.

CD8+ T-cell: Cytotoxic lymphocyte subtype that can mediate targeted cell death.

Granzyme B: Protease released by cytotoxic lymphocytes, inducing apoptosis in target cells.

Postcontrast FLAIR MRI: Fluid-attenuated inversion recovery sequence performed after contrast administration, used to detect meningeal and parenchymal enhancement.

References

1. Susac syndrome: neurological update (clinical features, long-term observational follow-up and management of sixteen patients). Journal of Neurology (2023).
2. Risk factors for severe hearing loss in Susac syndrome: A national cohort study. European Journal of Neurology (2024).
3. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome. Nature Communications (2019).
4. Diagnosis and Prediction of Relapses in Susac Syndrome: A New Use for MR Postcontrast FLAIR Leptomeningeal Enhancement. American Journal of Neuroradiology (2019).