Sir,

Pseudoxanthoma elasticum (PXE) is an inherited multisystem disorder that is associated with accumulation of mineralised and fragmented elastic and collagenous fibres in the skin, vascular walls, and Bruch's membrane in the eye.1, 2 Besides cardiovascular and skin pathologies, patients show characteristic lesions of the posterior segment of the eye, including peau d’orange, angioid streaks, chorioretinal atrophies such as comet tail lesions, and choroidal neovascularisation (CNV). There is yet no causal therapy for the gene defect (ABCC6 gene on chromosome 16p13.1) and its presumed metabolic consequences.1 However, the frequently occurring secondary CNVs can now be effectively treated with intravitreally administered anti-VEGF agents.3

A 44-year-old female patient suffering from PXE (confirmed by skin biopsy and genetic analysis) complained about gradually increasing blurred vision for the past 3–4 months in both eyes. Her best corrected visual acuity was 20/32 in the right eye and 20/63 in the left eye. An active CNV in the left eye was confirmed on fluorescein angiography (FA) and was treated with an intravitreal injection of 0.5 mg ranibizumab. At follow-up 1 month later, the CNV was inactive and visual acuity had increased to 20/50. Notably, a diffuse leakage at the posterior pole extending just beyond the vascular arcades of the left eye and not associated with the CNV had as well disappeared (Figure 1). On an indocyanin green angiography at baseline, no signs of an occult neovascularisation had been observed within the area of diffuse leakage on FA.

Figure 1
figure 1

(a) Fundus photography of the patient, showing areas of atrophy and hyperpigmentation adjacent to the papilla and angioid streaks. (c) Late-phase fluorescein angiography shows localised leakage in the lower temporal macula adjacent to an area of atrophy that is visible in (a) (marked by the black arrow head), as well as diffuse leakage, especially in the area of the upper and lower vascular arcade (white arrows); a high-resolution OCT scan ((b), localisation of the scan indicated by the green arrow in (c)) through the lower area of diffuse leakage shows an intact RPE/Bruch's membrane layer and no signs of neovascularisation; (d) 1 month after intravitreal injection of ranibizumab, the localised as well as diffuse leakage is considerably reduced in late-phase angiography (both FAs late phase between 11–13 min).

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The diffuse VEGF-dependent leakage provides further evidence for a generalised alteration of the Bruch's membrane–retinal pigment epithelium (RPE) complex in patients with PXE. The barrier function of the RPE was shown to be VEGF dependent.4 Possibly, PXE-associated alterations of Bruch's membrane render the overlying RPE more vulnerable to VEGF effects, resulting in diffuse leakage because of increased VEGF levels.5 The abnormal VEGF level involved in the development of the CNV may therefore have further increased the RPE-layer permeability in this case.

In conclusion, diffuse fluorescein leakage in the absence of vascular pathology may indicate alterations in the barrier function of the RPE in patients with PXE.