Abstract
Purpose
To investigate predictors for macular atrophy (MA) involving the fovea after photodynamic therapy (PDT) followed by pro re nata (PRN) treatment for polypoidal choroidal vasculopathy (PCV).
Methods
This prospective observational study analysed treatment-naïve eyes with symptomatic PCV without MA at baseline which were followed up for 5 years. All eyes were initially treated with PDT, followed by a PRN regimen of anti-vascular endothelial growth factor (VEGF) therapy and/or PDT. We assigned eyes with and eyes without development of MA involving the fovea 5 years after the initial treatment into MA and non-MA groups, respectively. Baseline parameters and the number of treatments were compared between the two groups.
Results
Seventy-two eyes of 69 consecutive patients were included, and 29 eyes of 29 patients were analysed. Twelve (41%) and 17 (59%) eyes were assigned into the MA and non-MA groups, respectively. There were significant differences in subfoveal choroidal thickness (226.2 ± 47.8 μm vs. 278.8 ± 68.1 μm, P = 0.03) and number of anti-VEGF injections (13.7 ± 9.6 vs. 5.4 ± 5.6, P = 0.007) between the MA and non-MA groups, but not in the number of PDT sessions (P = 0.71). Best-corrected visual acuity at 5 years in the MA group was lower than in the non-MA group (P = 0.048).
Conclusion
Our long-term observation suggests that a thin subfoveal choroid at baseline and many followed anti-VEGF injections in a PRN regimen increase the risk for development of MA involving the fovea 5 years after PDT.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Data availability
The datasets analysed during the current study are available from the corresponding author on reasonable request.
References
Yannuzzi LA, Sorenson J, Spaide RF, Lipson B. Idiopathic polypoidal choroidal vasculopathy (IPCV). Retina 1990;10:1–8.
Terasaki H, Miyake Y, Suzuki T, Nakamura M, Nagasaka T. Polypoidal choroidal vasculopathy treated with macular translocation: clinical pathological correlation. Br J Ophthalmol. 2002;86:321–7.
Matsuoka M, Ogata N, Otsuji T, Nishimura T, Takahashi K, Matsumura M. Expression of pigment epithelium derived factor and vascular endothelial growth factor in choroidal neovascular membranes and polypoidal choroidal vasculopathy. Br J Ophthalmol. 2004;88:809–15.
Hata M, Tsujikawa A, Miyake M, Yamashiro K, Ooto S, Oishi A, et al. Two-year visual outcome of ranibizumab in typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefe’s Arch Clin Exp Ophthalmol. 2015;253:221–7.
Kim JH, Kim JW, Kim CG, Lee DW. Long-term switching between ranibizumab and aflibercept in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Graefe’s Arch Clin Exp Ophthalmol. 2020;258:1677–85.
Yamamoto A, Okada AA, Kano M, Koizumi H, Saito M, Maruko I, et al. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Ophthalmology 2015;122:1866–72.
Chan W-M, Lam DSC, Lai TYY, Liu DTL, Li KKW, Yao Y, et al. Photodynamic therapy with verteporfin for symptomatic polypoidal choroidal vasculopathy: one-year results of a prospective case series. Ophthalmology 2004;111:1576–84.
Gomi F, Ohji M, Sayanagi K, Sawa M, Sakaguchi H, Oshima Y, et al. One-year outcomes of photodynamic therapy in age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese patients. Ophthalmology 2008;115:141–6.
Lai TYY, Lee GKY, Luk FOJ, Lam DSC. Intravitreal ranibizumab with or without photodynamic therapy for the treatment of symptomatic polypoidal choroidal vasculopathy. Retina 2011;31:1581–8.
Takayama K, Kaneko H, Kataoka K, Hattori K, Ra E, Tsunekawa T, et al. Comparison between 1-year outcomes of aflibercept with and without photodynamic therapy for polypoidal choroidal vasculopathy: Retrospective observation study. PLoS ONE. 2017;12:e0176100.
Schmidt-Erfurth U, Laqua H, Schlötzer-Schrehard U, Viestenz A, Naumann GOH. Histopathological changes following photodynamic therapy in human eyes. Arch Ophthalmol. 2002;120:835–44.
Schmidt-Erfurth U, Michels S, Barbazetto I, Laqua H. Photodynamic effects on choroidal neovascularization and physiological choroid. Investig Ophthalmol Vis Sci. 2002;43:830–41.
Miyata M, Ooto S, Yamashiro K, Tamura H, Hata M, Ueda-Arakawa N, et al. Five-year visual outcomes after anti-VEGF therapy with or without photodynamic therapy for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2019;103:617–22.
Cho HJ, Kim K, Lim SH, Kang DH, Kim JW. Retinal pigment epithelial atrophy after anti-vascular endothelial growth factor therapy for polypoidal choroidal vasculopathy. Br J Ophthalmol. 2020;104:1443–7.
Abdelfattah NS, Zhang H, Boyer DS, Sadda SR. Progression of macular atrophy in patients with neovascular age-related macular degeneration undergoing antivascular endothelial growth factor therapy. Retina 2016;36:1843–50.
Kuroda Y, Yamashiro K, Ooto S, Tamura H, Oishi A, Nakanishi H, et al. Macular atrophy and macular morphology in aflibercept-treated neovascular age-related macular degeneration. Retina 2018;38:1743–50.
Kuroda Y, Yamashiro K, Tsujikawa A, Ooto S, Tamura H, Oishi A, et al. Retinal pigment epithelial atrophy in neovascular age-related macular degeneration after ranibizumab treatment. Am J Ophthalmol. 2016;161:94–103.
Hata M, Yamashiro K, Oishi A, Ooto S, Tamura H, Miyata M, et al. Retinal pigment epithelial atrophy after anti–vascular endothelial growth factor injections for retinal angiomatous proliferation. Retina 2017;37:2069–77.
Hikichi T, Kitamei H, Shioya S. Retinal pigment epithelial atrophy over polypoidal choroidal vasculopathy lesions during ranibizumab monotherapy. BMC Ophthalmol. 2016;16:55 https://doi.org/10.1186/s12886-016-0237-x
Chung SE, Kang SW, Lee JH, Kim YT. Choroidal thickness in polypoidal choroidal vasculopathy and exudative age-related macular degeneration. Ophthalmology 2011;118:840–5.
Kim S-W, Oh J, Kwon S-S, Yoo J, Huh K. Comparison of choroidal thickness among patients with healthy eyes, early age-related maculopathy, neovascular age-related macular degeneration, central serous chorioretinopathy, and polypoidal choroidal vasculopathy. Retina 2011;31:1904–11.
Ford KM, Saint-Geniez M, Walshe T, Zahr A, D’Amore PA. Expression and role of VEGF in the adult retinal pigment epithelium. Investig Ophthalmol Vis Sci. 2011;52:9478–87.
Sadda SR, Tuomi LL, Ding B, Fung AE, Hopkins JJ. Macular atrophy in the HARBOR study for neovascular age-related macular degeneration. Ophthalmology 2018;125:878–86.
Chakravarthy U, Harding SP, Rogers CA, Downes S, Lotery AJ, Dakin HA, et al. A randomised controlled trial to assess the clinical effectiveness and cost-effectiveness of alternative treatments to Inhibit VEGF in Age-related choroidal Neovascularisation (IVAN). Health Technol Assess. 2015;19:1.
Sadda SR, Guymer R, Monés JM, Tufail A, Jaffe GJ. Anti–vascular endothelial growth factor use and atrophy in neovascular age-related macular degeneration: Systematic Literature Review and Expert Opinion. Ophthalmology 2020;127:648–59.
Bhisitkul RB, Mendes TS, Rofagha S, Enanoria W, Boyer DS, Sadda SR, et al. Macular atrophy progression and 7-year vision outcomes in subjects from the ANCHOR, MARINA, and HORIZON studies: the SEVEN-UP study∗. Am J Ophthalmol. 2015;159:915–24.
Schlötzer-Schrehardt U, Viestenz A, Naumann GOH, Laqua H, Michels S, Schmidt-Erfurth U. Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes. Graefe’s Arch Clin Exp Ophthalmol. 2002;240:748–57.
Nassisi M, Lavia C, Alovisi C, Musso L, Eandi CM. Short-term choriocapillaris changes in patients with central serous chorioretinopathy after half-dose photodynamic therapy. Int J Mol Sci. 2017;18:2468 https://doi.org/10.3390/ijms18112468
Bhutto I, Lutty G. Understanding age-related macular degeneration (AMD): Relationships between the photoreceptor/retinal pigment epithelium/Bruch’s membrane/choriocapillaris complex. Mol Asp Med. 2012;33:295–317.
Miyamoto N, Mandai M, Oishi A, Nakai S, Honda S, Hirashima T, et al. Long-term results of photodynamic therapy or ranibizumab for polypoidal choroidal vasculopathy in LAPTOP study. Br J Ophthalmol. 2019;103:844–8.
Wataru K, Sugiyama A, Yoneyama S, Matsubara M, Fukuda Y, Parikh R, et al. Five-year outcomes of photodynamic therapy combined with intravitreal injection of ranibizumab or aflibercept for polypoidal choroidal vasculopathy. PLoS ONE. 2020;15:e0229231 https://doi.org/10.1371/journal.pone.0229231
Miyata M, Hata M, Ooto S, Ogino K, Gotoh N, Morooka S, et al. Choroidal and retinal atrophy of Bietti crystalline dystrophy patients with CYP4V2 mutations compared to retinitis pigmentosa patients with EYS mutations. Retina 2017;37:1193–202.
Akagi-Kurashige Y, Tsujikawa A, Yuzawa M, Ishibashi T, Nakanishi H, Nakatani E, et al. A 5-year multicenter prospective cohort study on the long-term visual prognosis and predictive factors for visual outcome in Japanese patients with age-related macular degeneration: the AMD2000 study. Jpn J Ophthalmol. 2018;62:137–43.
Funding
This work was supported in part by a grant-in-aid for scientific research (no. 18K09444 and no. 21K09716) from the Japan Society for the Promotion of Science, Tokyo, Japan. This organization had no role in the design or conduct of this research.
Author information
Authors and Affiliations
Contributions
KK is responsible for the study design and writing the paper, MM is responsible for study design, data acquisition, and writing the paper. SO, HT, NUA, AT, AU, YM, MM, KY and AT are responsible for data acquisition and review of the paper.
Corresponding author
Ethics declarations
Competing interests
All authors attest that they meet the current ICMJE criteria for authorship.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Kawai, K., Miyata, M., Ooto, S. et al. Macular atrophy at 5 years after photodynamic therapy for polypoidal choroidal vasculopathy. Eye 37, 1067–1072 (2023). https://doi.org/10.1038/s41433-022-02067-6
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/s41433-022-02067-6
This article is cited by
-
Efficacy of aflibercept combined with 80% dose photodynamic therapy for pachychoroid neovasculopathy
Scientific Reports (2025)
-
Incidence of recurrence and development of polypoidal lesions following half-dose and two-thirds dose photodynamic therapy for pachychoroid neovasculopathy
Scientific Reports (2025)
-
Long-term observational data on neovascular age-related macular degeneration: a 10-year follow-up study
International Ophthalmology (2025)
-
Increased macular atrophy area with photodynamic therapy over intravitreal aflibercept at 2-year follow-up of pachychoroid neovasculopathy
Japanese Journal of Ophthalmology (2025)
-
Three-year outcome of photodynamic therapy combined with VEGF inhibitor for pachychoroid neovasculopathy
Graefe's Archive for Clinical and Experimental Ophthalmology (2024)
