Skip to main content
Top
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 2/2020

Open Access 01-02-2020 | Aflibercept | Retinal Disorders

Aflibercept for choroidal neovascularizations secondary to pseudoxanthoma elasticum: a prospective study

Authors: Martin Gliem, Johannes Birtel, Philipp Herrmann, Rolf Fimmers, Moritz Berger, Christoph Coch, Almut Wingen, Frank G. Holz, Peter Charbel Issa

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 2/2020

Login to get access

Abstract

Purpose

To evaluate the use of 2 mg intravitreal aflibercept for treatment of choroidal neovascularization (CNV) secondary to angioid streaks in patients with pseudoxanthoma elasticum (PXE).

Methods

In this 12-month prospective, open-label, uncontrolled, non-randomized interventional clinical trial, 15 PXE patients with CNV (mean age: 53 years, range 22–65) received one initial intravitreal injection of 2 mg aflibercept. Further injections were based on CNV activity at monthly examinations. The primary endpoint was change of best corrected visual acuity (BCVA) after 12 months. Secondary outcomes were change of central retinal thickness (CRT), leakage from CNV, retinal sensitivity, and vision-related quality of life.

Results

BCVA improved from 75.0 ± 10.8 (± SD, Snellen equivalent 20/32) to 79.3 ± 7.3 ETDRS letters (20/32) at final visit (p = 0.083). CRT decreased from 317 ± 81 to 279 ± 51 μm (p = 0.004). Retinal sensitivity on microperimetry changed from 17.8 ± 4.5 to 18.5 ± 4.3 dB (p = 0.103) and vision-related quality of life from a VQF-25 score of 80.7 ± 10.4 to 83.5 ± 14.5 (p = 0.554). The mean number of injections was 6.7 ± 2.6, and 5 participants had persistent or reactivated CNV activity at final visit. The observed adverse events were comparable with studies on aflibercept for other indications.

Conclusion

The results of this study indicate that intravitreal aflibercept is a treatment option for CNV secondary to PXE.
Literature
1.
go back to reference Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, Pasquali-Ronchetti I, Pope FM, Richards A, Terry S, Bercovitch L, de Paepe A, Boyd CD (2000) Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 25:223–227CrossRef Le Saux O, Urban Z, Tschuch C, Csiszar K, Bacchelli B, Quaglino D, Pasquali-Ronchetti I, Pope FM, Richards A, Terry S, Bercovitch L, de Paepe A, Boyd CD (2000) Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Nat Genet 25:223–227CrossRef
2.
go back to reference Le Saux O, Martin L, Aherrahrou Z, Leftheriotis G, Váradi A, Brampton CN (2012) The molecular and physiological roles of ABCC6: more than meets the eye. Front Genet 3:289PubMedPubMedCentral Le Saux O, Martin L, Aherrahrou Z, Leftheriotis G, Váradi A, Brampton CN (2012) The molecular and physiological roles of ABCC6: more than meets the eye. Front Genet 3:289PubMedPubMedCentral
3.
go back to reference Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, Plomp A, Bergen AA, Oude Elferink RPJ, Borst P, van de Wetering K (2014) ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol 34:1985–1989CrossRef Jansen RS, Duijst S, Mahakena S, Sommer D, Szeri F, Váradi A, Plomp A, Bergen AA, Oude Elferink RPJ, Borst P, van de Wetering K (2014) ABCC6-mediated ATP secretion by the liver is the main source of the mineralization inhibitor inorganic pyrophosphate in the systemic circulation-brief report. Arterioscler Thromb Vasc Biol 34:1985–1989CrossRef
4.
go back to reference Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IEM, Bergen AAB, Gorgels TGMF, Borst P, van de Wetering K (2013) ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A 110:20206–20211CrossRef Jansen RS, Küçükosmanoglu A, de Haas M, Sapthu S, Otero JA, Hegman IEM, Bergen AAB, Gorgels TGMF, Borst P, van de Wetering K (2013) ABCC6 prevents ectopic mineralization seen in pseudoxanthoma elasticum by inducing cellular nucleotide release. Proc Natl Acad Sci U S A 110:20206–20211CrossRef
5.
go back to reference Charbel Issa P, Finger RP, Götting C, Hendig D, Holz FG, Scholl HPN (2010) Centrifugal fundus abnormalities in pseudoxanthoma elasticum. Ophthalmology 117:1406–1414CrossRef Charbel Issa P, Finger RP, Götting C, Hendig D, Holz FG, Scholl HPN (2010) Centrifugal fundus abnormalities in pseudoxanthoma elasticum. Ophthalmology 117:1406–1414CrossRef
6.
go back to reference Charbel Issa P, Finger RP, Holz FG, Scholl HPN (2009) Multimodal imaging including spectral domain OCT and confocal near infrared reflectance for characterization of outer retinal pathology in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 50:5913–5918CrossRef Charbel Issa P, Finger RP, Holz FG, Scholl HPN (2009) Multimodal imaging including spectral domain OCT and confocal near infrared reflectance for characterization of outer retinal pathology in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 50:5913–5918CrossRef
7.
go back to reference Gliem M, de Zaeytijd J, Finger RP, Holz FG, Leroy BP, Charbel Issa P (2013) An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet 4:14CrossRef Gliem M, de Zaeytijd J, Finger RP, Holz FG, Leroy BP, Charbel Issa P (2013) An update on the ocular phenotype in patients with pseudoxanthoma elasticum. Front Genet 4:14CrossRef
8.
go back to reference Gliem M, Müller PL, Birtel J, Hendig D, Holz FG, Charbel Issa P (2016) Frequency, phenotypic characteristics and progression of atrophy associated with a diseased Bruch’s membrane in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 57:3323CrossRef Gliem M, Müller PL, Birtel J, Hendig D, Holz FG, Charbel Issa P (2016) Frequency, phenotypic characteristics and progression of atrophy associated with a diseased Bruch’s membrane in pseudoxanthoma elasticum. Invest Ophthalmol Vis Sci 57:3323CrossRef
9.
go back to reference Birtel J, Lindner M, Mishra DK, Müller PL, Hendig D, Herrmann P, Holz FG, Fleckenstein M, Gliem M, Charbel Issa P (2019) Retinal imaging including optical coherence tomography angiography for detecting active choroidal neovascularization in pseudoxanthoma elasticum. Clin Exp Ophthalmol 47:240–249CrossRef Birtel J, Lindner M, Mishra DK, Müller PL, Hendig D, Herrmann P, Holz FG, Fleckenstein M, Gliem M, Charbel Issa P (2019) Retinal imaging including optical coherence tomography angiography for detecting active choroidal neovascularization in pseudoxanthoma elasticum. Clin Exp Ophthalmol 47:240–249CrossRef
10.
go back to reference Gliem M, Finger RP, Fimmers R, Brinkmann CK, Holz FG, Charbel Issa P (2013) Treatment of choroidal neovascularization due to angioid streaks: a comprehensive review. Retina 33:1300–1314CrossRef Gliem M, Finger RP, Fimmers R, Brinkmann CK, Holz FG, Charbel Issa P (2013) Treatment of choroidal neovascularization due to angioid streaks: a comprehensive review. Retina 33:1300–1314CrossRef
11.
go back to reference Finger RP, Fenwick E, Marella M, Charbel Issa P, Scholl HPN, Holz FG, Lamoureux EL (2011) The relative impact of vision impairment and cardiovascular disease on quality of life: the example of pseudoxanthoma elasticum. Health Qual Life Outcomes 9:113CrossRef Finger RP, Fenwick E, Marella M, Charbel Issa P, Scholl HPN, Holz FG, Lamoureux EL (2011) The relative impact of vision impairment and cardiovascular disease on quality of life: the example of pseudoxanthoma elasticum. Health Qual Life Outcomes 9:113CrossRef
12.
go back to reference Risseeuw S, Ossewaarde-van Norel J, Klaver CCW, Colijn JM, Imhof SM, van Leeuwen R (2018) Visual acuity in pseudoxanthoma elasticum. Retina (Philadelphia, Pa) Risseeuw S, Ossewaarde-van Norel J, Klaver CCW, Colijn JM, Imhof SM, van Leeuwen R (2018) Visual acuity in pseudoxanthoma elasticum. Retina (Philadelphia, Pa)
13.
go back to reference Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99:11393–11398CrossRef Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci U S A 99:11393–11398CrossRef
14.
go back to reference Nguyen QD, Shah SM, Hafiz G, Quinlan E, Sung J, Chu K, Cedarbaum JM, Campochiaro PA (2006) A phase I trial of an IV-administered vascular endothelial growth factor trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmology 113:1522.e1–1522.e14CrossRef Nguyen QD, Shah SM, Hafiz G, Quinlan E, Sung J, Chu K, Cedarbaum JM, Campochiaro PA (2006) A phase I trial of an IV-administered vascular endothelial growth factor trap for treatment in patients with choroidal neovascularization due to age-related macular degeneration. Ophthalmology 113:1522.e1–1522.e14CrossRef
15.
go back to reference Heier JS, Brown DM, Chong V, Korobelnik J-F, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548CrossRef Heier JS, Brown DM, Chong V, Korobelnik J-F, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U (2012) Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 119:2537–2548CrossRef
16.
go back to reference Ikuno Y, Ohno-Matsui K, Wong TY, Korobelnik J-F, Vitti R, Li T, Stemper B, Asmus F, Zeitz O, Ishibashi T (2015) Intravitreal Aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study. Ophthalmology 122:1220–1227CrossRef Ikuno Y, Ohno-Matsui K, Wong TY, Korobelnik J-F, Vitti R, Li T, Stemper B, Asmus F, Zeitz O, Ishibashi T (2015) Intravitreal Aflibercept injection in patients with myopic choroidal neovascularization: the MYRROR study. Ophthalmology 122:1220–1227CrossRef
17.
go back to reference Diago T (2016) Treat and extend regimen with aflibercept for choroidal neovascularization in angioid streaks. Eye 30:637–639CrossRef Diago T (2016) Treat and extend regimen with aflibercept for choroidal neovascularization in angioid streaks. Eye 30:637–639CrossRef
18.
go back to reference Esen E, Sizmaz S, Demircan N (2015) Intravitreal aflibercept for management of subfoveal choroidal neovascularization secondary to angioid streaks. Indian J Ophthalmol 63:616–618CrossRef Esen E, Sizmaz S, Demircan N (2015) Intravitreal aflibercept for management of subfoveal choroidal neovascularization secondary to angioid streaks. Indian J Ophthalmol 63:616–618CrossRef
19.
go back to reference Tetikoglu M, Sagdik HM, Aktas S, Ozcura F (2016) Intravitreal aflibercept for refractory choroidal neovascularization secondary to angioid streaks. Eye 30:894–895CrossRef Tetikoglu M, Sagdik HM, Aktas S, Ozcura F (2016) Intravitreal aflibercept for refractory choroidal neovascularization secondary to angioid streaks. Eye 30:894–895CrossRef
20.
go back to reference Vaz-Pereira S, Collaço L, de Salvo G, van Zeller P (2015) Intravitreal aflibercept for choroidal neovascularisation in angioid streaks. Eye 29:1236–1238CrossRef Vaz-Pereira S, Collaço L, de Salvo G, van Zeller P (2015) Intravitreal aflibercept for choroidal neovascularisation in angioid streaks. Eye 29:1236–1238CrossRef
22.
go back to reference Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD (2001) Development of the 25-item national eye institute visual function questionnaire. Arch Ophthalmol 119:1050–1058CrossRef Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD (2001) Development of the 25-item national eye institute visual function questionnaire. Arch Ophthalmol 119:1050–1058CrossRef
23.
go back to reference Finger RP, Charbel Issa P, Hendig D, Scholl HPN, Holz FG (2011) Monthly ranibizumab for choroidal neovascularizations secondary to angioid streaks in pseudoxanthoma elasticum: a one-year prospective study. Am J Ophthalmol 152:695–703CrossRef Finger RP, Charbel Issa P, Hendig D, Scholl HPN, Holz FG (2011) Monthly ranibizumab for choroidal neovascularizations secondary to angioid streaks in pseudoxanthoma elasticum: a one-year prospective study. Am J Ophthalmol 152:695–703CrossRef
24.
go back to reference Lai TYY, Staurenghi G, Lanzetta P, Holz FG, Melissa Liew SH, Desset-Brethes S, Staines H, Hykin PG (2018) Efficacy and safety of ranibizumab for the treatment of choroidal neovascularization due to uncommon cause: twelve-month results of the MINERVA study. Retina 38:1464–1477CrossRef Lai TYY, Staurenghi G, Lanzetta P, Holz FG, Melissa Liew SH, Desset-Brethes S, Staines H, Hykin PG (2018) Efficacy and safety of ranibizumab for the treatment of choroidal neovascularization due to uncommon cause: twelve-month results of the MINERVA study. Retina 38:1464–1477CrossRef
25.
go back to reference Lefthériotis G, Omarjee L, Le Saux O, Henrion D, Abraham P, Prunier F, Willoteaux S, Martin L (2013) The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification. Front Genet 4:4CrossRef Lefthériotis G, Omarjee L, Le Saux O, Henrion D, Abraham P, Prunier F, Willoteaux S, Martin L (2013) The vascular phenotype in Pseudoxanthoma elasticum and related disorders: contribution of a genetic disease to the understanding of vascular calcification. Front Genet 4:4CrossRef
26.
go back to reference Gliem M, Birtel J, Müller PL, Hendig D, Faust I, Herrmann P, Holz FG, Adamus G, Charbel Issa P (2019) Acute Retinopathy in Pseudoxanthoma Elasticum. JAMA Ophthalmol 137:1165–1173CrossRef Gliem M, Birtel J, Müller PL, Hendig D, Faust I, Herrmann P, Holz FG, Adamus G, Charbel Issa P (2019) Acute Retinopathy in Pseudoxanthoma Elasticum. JAMA Ophthalmol 137:1165–1173CrossRef
Metadata
Title
Aflibercept for choroidal neovascularizations secondary to pseudoxanthoma elasticum: a prospective study
Authors
Martin Gliem
Johannes Birtel
Philipp Herrmann
Rolf Fimmers
Moritz Berger
Christoph Coch
Almut Wingen
Frank G. Holz
Peter Charbel Issa
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 2/2020
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-019-04551-4

Other articles of this Issue 2/2020

Graefe's Archive for Clinical and Experimental Ophthalmology 2/2020 Go to the issue