Sir,

We welcome, and read with interest, the systematic review of Purtscher retinopathies by Miguel et al,1 who described the systemic aetiologies underlying Purtscher’s, the clinical features, the efficacy of corticosteroid therapy, and visual outcomes.

The discovery of effective therapies for Purtscher-spectrum retinopathies requires identification of the mechanism underlying Purtscher-related microvasculopathy. Despite the sporadic treatment of Purtscher’s with corticosteroids, only 8 of the 17 Purtscher-associated aetiologies identified by the authors are primary inflammatory disorders, 5 of which necessitate systemic steroid therapy (Table 1). Ocular inflammation is not a feature of Purtscher retinopathies.

Table 1 Causes of Purtscher retinopathies, inflammation, and thrombotic microangiopathy
Full size table

We observed that 14 Purtscher-associated aetiologies were recognized precipitants of thrombotic microangiopathy (TMA) (Table 1)—a systemic syndrome that triggers widespread microvascular thrombosis in response to a range of primary disorders.2 Ocular features of Purtscher’s include cotton wool spots, retinal haemorrhages, Purtscher-flecken, and arteriolar obstruction with late leakage on fluorescein angiography.1 Thrombotic microangiopathy may account for all features through terminal arteriole and capillary hyaline thrombosis—pathological hallmarks identified in patients as early as 1924.2

The molecular pathophysiology of TMA is heterogeneous, varying according to systemic aetiology. TMA involves a complex, interdependent dysregulation of haemostatic, thrombotic, and complement cascades with endothelial dysfunction and inflammation—corticosteroids address only the inflammatory component. Research efforts have identified decreased activity of ADAMTS-13, a von Willebrand clotting factor, in association with TTP3 and HELLP syndrome4 and antibodies against CD36, the ADAMTS-13 endothelial receptor in haemolytic uraemic syndrome. Novel molecules offer fresh therapeutic targets;2 recent reports suggest success in depleting the ADAMTS-13 antibody in TTP with the novel biologic agent Bortezomib.5

The lack of efficacy demonstrated with corticosteroids is logical given the diverse aetiologies of Purtscher’s, which may demonstrate a primary inflammatory trigger, such as acute pancreatitis, but later perpetuate through consumptive thrombocytopenia, coagulopathy, and/or complement activation associated with TMA. These secondary processes are unlikely to be steroid responsive.

We suggest consideration of the hypothesis that Purtscher retinopathies are manifestations of thrombotic microangiopathy. Research into the molecular pathogenesis of TMAs with identification of novel molecules in physiological and pathological cascades—such as ADAMTS-13—may offer more promising therapeutic targets for future patients with Purtscher retinopathies.