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. 2019 Oct 1;137(10):1165-1173.
doi: 10.1001/jamaophthalmol.2019.2910.

Acute Retinopathy in Pseudoxanthoma Elasticum

Martin Gliem  1   2   3   4 , Johannes Birtel  1   2 , Philipp L Müller  1   2 , Doris Hendig  5 , Isabel Faust  5 , Philipp Herrmann  1   2 , Frank G Holz  1   2 , Grazyna Adamus  6 , Peter Charbel Issa  1   2   3   4
Affiliations

Acute Retinopathy in Pseudoxanthoma Elasticum

Martin Gliem et al. JAMA Ophthalmol. .

Erratum in

  • Errors in Abstract, Text, and Figure.
    [No authors listed] [No authors listed] JAMA Ophthalmol. 2019 Oct 1;137(10):1211. doi: 10.1001/jamaophthalmol.2019.3583. JAMA Ophthalmol. 2019. PMID: 31465097 Free PMC article. No abstract available.

Abstract

Importance: Acute retinopathy may partly explain variable disease manifestation and vision loss in patients with pseudoxanthoma elasticum (PXE). The diagnosis of this likely autoimmune process may inform patient counseling and treatment approaches.

Objective: To characterize acute retinopathy in patients with PXE as a disease manifestation that may be associated with profound visual impairment.

Design, setting, and participants: This single-center case series was conducted from May 2013 to October 2018. It used the patient database of the Department of Ophthalmology at the University of Bonn, a referral center for PXE in Germany. Patients at this center with genetically confirmed PXE and who met the inclusion criteria were included (n = 9). Patients underwent multimodal retinal imaging, including fundus photography, fundus autofluorescence (AF), optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA); in select cases, electroretinography as well as antiretinal and anti-retinal pigment epithelium (RPE) antibody testing were also used.

Main outcomes and measures: Clinical presentation and disease course.

Results: Nine patients (8 [89%] female; mean [range] age, 43 [19-55] years) with acute retinopathy were identified in a cohort of 167 consecutive patients with PXE (frequency of 5%). Symptoms ranged from light sensations or metamorphopsia to profound vision loss. Visual acuity was reduced in 6 patients (67%), ranging from a best-corrected visual acuity of 20/30 to perception of hand movements at manifestation. All patients revealed characteristic fundus features with temporary appearance of partly confluent outer retinal whitish dots at the posterior pole, which corresponded to areas of hyperautofluorescence on fundus AF, loss of the ellipsoid band on OCT, and associated scotomata. The FA and late-phase ICGA imaging showed associated hyperfluorescence and hypocyanescence. Electroretinography revealed a variable reduction of amplitudes. Changes were fully reversible within 1 month in 3 of 8 patients with available follow-up data. Of the remaining 5 patients, 3 had a prolonged and likely permanent vision loss (observation period, 1-64 months) mainly owing to central subretinal hyperreflective material originating from angioid streaks. In 4 (67%) of 6 tested, antiretinal and/or anti-RPE antibodies were detected.

Conclusions and relevance: Acute retinopathy in patients with PXE may occur, with symptoms ranging from short-term, reversible alterations to irreversible vision loss; these findings contribute to understanding the variable ocular disease progression in PXE and provide insights into the autoimmune phenomena of the posterior pole.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Gliem reported receiving grants from the University of Bonn and German Research Foundation, nonfinancial support from Heidelberg Engineering during the conduct of the study, personal fees from Bayer Healthcare, and grants from Heidelberg Engineering outside of the submitted work. Dr Müller reported receiving grants from the Association of Rhine-Westphalian Ophthalmologists, German Research Foundation, and BONFOR research program of the University of Bonn as well as nonfinancial support from Heidelberg Engineering, Optos, CenterVue, and Carl-Zeiss Meditec during the conduct of the study. Dr Holz reported receiving grants, personal fees, and nonfinancial support from Heidelberg Engineering; personal fees and nonfinancial support from Zeiss during the conduct of the study; and grants from CenterVue and Optos outside of the submitted work. Dr Charbel Issa reported receiving grants from the National Institute for Health Research, Oxford Biomedical Research Centre, and ProRetina during the conduct of the study; personal fees from Inozyme; grants and nonfinancial support from Bayer; and nonfinancial support from Heidelberg Engineering outside of the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Retinal Phenotype of Patient 1 With Pseudoxanthoma Elasticum and Acute Retinopathy
The white line in A illustrates the position of the OCT section in D. The white arrowheads in D mark areas of ellipsoid zone loss. ICGA indicates indocyanine green angiography.
Figure 2.
Figure 2.. Retinal Phenotype of Patient 2 With Pseudoxanthoma Elasticum and Acute Retinopathy
The white line in A illustrates the position of the OCT section in D. The white arrowhead in D points to the subretinal hyperreflective material with adjacent hyperreflectivity of the outer retina. ICGA indicates indocyanine green angiography.
Figure 3.
Figure 3.. Retinal Phenotype of Patient 3 With Pseudoxanthoma Elasticum and Acute Retinopathy
The white line in A illustrates the position of the OCT section in D. The white arrowhead in B points to dotlike alterations. ICGA indicates indocyanine green angiography.
See this image and copyright information in PMC

References

    1. Le Saux O, Urban Z, Tschuch C, et al. . Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet. 2000;25(2):223-227. doi:10.1038/76102 - DOI - PubMed
    1. Le Saux O, Martin L, Aherrahrou Z, Leftheriotis G, Váradi A, Brampton CN. The molecular and physiological roles of ABCC6: more than meets the eye. Front Genet. 2012;3:289. doi:10.3389/fgene.2012.00289 - DOI - PMC - PubMed
    1. Charbel Issa P, Finger RP, Götting C, Hendig D, Holz FG, Scholl HPN. Centrifugal fundus abnormalities in pseudoxanthoma elasticum. Ophthalmology. 2010;117(7):1406-1414. doi:10.1016/j.ophtha.2009.11.008 - DOI - PubMed
    1. Gliem M, Müller PL, Birtel J, Hendig D, Holz FG, Charbel Issa P. Frequency, phenotypic characteristics and progression of atrophy associated with a diseased Bruch’s membrane in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci. 2016;57(7):3323-3330. doi:10.1167/iovs.16-19388 - DOI - PubMed
    1. Gliem M, Zaeytijd JD, Finger RP, Holz FG, Leroy BP, Charbel Issa P. An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet. 2013;4:14. doi:10.3389/fgene.2013.00014 - DOI - PMC - PubMed