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Randomized Controlled Trial
. 2020 Oct 20;15(10):e0240970.
doi: 10.1371/journal.pone.0240970. eCollection 2020.

The effect of etidronate on choroidal neovascular activity in patients with pseudoxanthoma elasticum

Sara Risseeuw  1 , Redmer van Leeuwen  1 , Saskia M Imhof  1 , Pim A de Jong  2 , Willem P Th M Mali  2 , Wilko Spiering  3 , Jeannette Ossewaarde-van Norel  1
Affiliations
Randomized Controlled Trial

The effect of etidronate on choroidal neovascular activity in patients with pseudoxanthoma elasticum

Sara Risseeuw et al. PLoS One. .

Abstract

Aim: To assess the effect of the bisphosphonate etidronate on choroidal neovascular (CNV) activity in patients with pseudoxanthoma elasticum (PXE).

Methods: This is an ancillary study in a single center, randomized, double-blind placebo-controlled trial (RCT) in which 74 patients with PXE were assigned to either one-year etidronate or placebo treatment. Spectral domain optical coherence tomography (SD-OCT) imaging and color fundus photography were performed every three months for one year and were systematically assessed on signs of CNV activity.

Results: In the etidronate group, 11 (30%) of the patients had CNV activity at baseline, compared to 25 (67%) of the patients in the placebo group (P = 0.005). The proportion of eyes with CNV activity during the study ranged from 18-33% in the etidronate group and 42-56% in the placebo group and no significant difference in improvement or worsening of CNV activity was found (P = 0.168). Using a generalized mixed model for repeated measures, there was a protective effect of etidronate in crude analysis (RR 0.86, 95% CI 0.75-0.98) that disappeared when adjusting for baseline CNV activity (RR 0.97, 95% CI 0.84-1.13).

Conclusion: In this post-hoc RCT analysis we did not observe a protecting or deteriorating effect of etidronate on CNV activity in patients with PXE after adjustment for baseline CNV.

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Conflict of interest statement

UNI-Pharma SA provided the etidronate and placebo capsules for free, but was not involved in the design, the execution, the analysis, or the reporting of the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Changes in CNV activity.
Optical coherence tomography (OCT) imaging of changes in CNV activity in patients with pseudoxanthoma elasticum with corresponding infrared image. The time interval between the study visit and the next visit is three months. The upper images (A and B) show an increase of subretinal fluid and outgrowth of the CNV complex and illustrates a worsening of CNV activity. In the middle (C and D), the CNV is inactive and stable. Below (E and F) a decrease of subretinal fluid is seen, illustrating an improvement of CNV activity.
Fig 2
Fig 2. Proportion of eyes with CNV activitya.
CNV; choroidal neovascularization. The white numbers represent the absolute number of eyes per group. a. CNV activity was diagnosed if at least one of the following criteria was present: hemorrhage in the posterior pole on color fundus photography, and/or intra- or subretinal fluid with signs of CNV nearby, and/or growth of a CNV complex.
Fig 3
Fig 3. Change in CNV activity in patients (n = 52) with at least one neovascular active period in one or both eyes during the trial.
a CNV; choroidal neovascularization. The white numbers represent the absolute number of eyes per group. a. Change in CNV activity was based on a subjective assessment of all B-scans compared to the previous examination.
See this image and copyright information in PMC

References

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