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Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal VasculopathyThe EVEREST II Randomized Clinical Trial

Educational Objective
To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt verteporfin photodynamic therapy combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with polypoidal choroidal vasculopathy for 24 months.
1 Credit CME
Key Points

Question  What are the differences in treatment outcomes of combination therapy with intravitreal ranibizumab and verteporfin photodynamic therapy vs ranibizumab monotherapy in polypoidal choroidal vasculopathy at month 24?

Findings  In the EVEREST II randomized clinical trial, combination therapy was superior to monotherapy in terms of adjusted mean best-corrected visual acuity gain and superior in achieving complete absence of indocyanine green hyperfluorescence of polypoidal lesions with fewer ranibizumab injections.

Meaning  These data suggest that ranibizumab plus prompt verteporfin photodynamic therapy is more effective compared with ranibizumab monotherapy for polypoidal choroidal vasculopathy with reduced treatment burden.

Abstract

Importance  The 2-year efficacy and safety of combination therapy of ranibizumab administered together with verteporfin photodynamic therapy (vPDT) compared with ranibizumab monotherapy in participants with polypoidal choroidal vasculopathy (PCV) are unclear.

Objective  To compare treatment outcomes of ranibizumab, 0.5 mg, plus prompt vPDT combination therapy with ranibizumab, 0.5 mg, monotherapy in participants with PCV for 24 months.

Design, Setting, and Participants  This 24-month, phase IV, double-masked, multicenter, randomized clinical trial (EVEREST II) was conducted among Asian participants from August 7, 2013, to March 2, 2017, with symptomatic macular PCV confirmed using indocyanine green angiography.

Interventions  Participants (N = 322) were randomized 1:1 to ranibizumab, 0.5 mg, plus vPDT (combination therapy group; n = 168) or ranibizumab, 0.5 mg, plus sham PDT (monotherapy group; n = 154). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT (combination group) or sham PDT (monotherapy group) on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions.

Main Outcomes and Measures  Evaluation of combination therapy vs monotherapy at 24 months in key clinical outcomes, treatment exposure, and safety. Polypoidal lesion regression was defined as the absence of indocyanine green hyperfluorescence of polypoidal lesions.

Results  Among 322 participants (mean [SD] age, 68.1 [8.8] years; 225 [69.9%] male), the adjusted mean best-corrected visual acuity (BCVA) gains at month 24 were 9.6 letters in the combination therapy group and 5.5 letters in the monotherapy group (mean difference, 4.1 letters; 95% CI, 1.0–7.2 letters; P = .005), demonstrating that combination therapy was superior to monotherapy by the BCVA change from baseline to month 24. Combination therapy was superior to monotherapy in terms of complete polypoidal lesion regression at month 24 (81 of 143 [56.6%] vs 23 of 86 [26.7%] participants; P < .001). Participants in the combination group received fewer ranibizumab injections (median, 6.0 [interquartile range (IQR), 4.0-11.0]) than the monotherapy group (median, 12.0 [IQR, 7.0-17.0]) up to month 24. The combination group required a median of 2.0 (IQR, 1.0-3.0) vPDT treatments for 24 months, with 75 of 168 participants (44.6%) requiring only 1 vPDT treatment.

Conclusions and Relevance  The 24-month data findings confirm that ranibizumab therapy, given as monotherapy or in combination with vPDT, is efficacious and safe for treatment of PCV. Combination therapy with vPDT added to ranibizumab achieved superior BCVA gain, increased odds of complete polypoidal lesion regression, and fewer treatment episodes compared with ranibizumab monotherapy.

Trial Registration  ClinicalTrials.gov Identifier: NCT01846273.

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Article Information

Accepted for Publication: May 15, 2020.

Published Online: July 16, 2020. doi:10.1001/jamaophthalmol.2020.2443

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2020 Lim TH et al. JAMA Ophthalmology.

Corresponding Author: Tock H. Lim, MBBS, National Healthcare Group Eye Institute, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433 (tock_han_lim@nhg.com.sg).

Author Contributions: Drs Patalauskaite and Margaron had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Lim, Lai, Wong, Chen, Tan, Lee, Ngah, Koh.

Acquisition, analysis, or interpretation of data: Lim, Lai, Takahashi, Wong, Chen, Ruamviboonsuk, Tan, Lee, Cheung, Patalauskaite, Margaron, Koh.

Drafting of the manuscript: Lim, Wong, Chen, Tan, Patalauskaite.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Patalauskaite, Margaron.

Administrative, technical, or material support: Chen, Ruamviboonsuk, Cheung, Ngah, Patalauskaite, Margaron, Koh.

Supervision: Lim, Takahashi, Ruamviboonsuk, Cheung, Margaron, Koh.

Conflict of Interest Disclosures: Dr Lim reported receiving grants from Tan Tock Seng Hospital during the conduct of the study; receiving travel reimbursement from Heidelberg Engineering, and being an advisory board member of Novartis, with honorarium and travel reimbursement being paid to his institution. Dr Lai reported receiving grants and personal fees from Bayer Healthcare, Chengdu KangHong Biotech, Novartis Pharma AG, and Roche during the conduct of the study; receiving grants from Bayer Healthcare, Novartis Pharma AG, Roche, and Santen; receiving lecture fees from Allergan, Bausch & Lomb, Bayer Healthcare, and Novartis Pharma AG; and being a consultant for Allergan, Bayer Healthcare, Boehringer Ingelheim, Genentech, Novartis Pharma AG, Oculis, and Roche outside the submitted work. Dr Takahashi reported receiving financial support from Alcon (Japan), Allergan (Japan), Bayer Healthcare, HOYA, KOWA, Kyowa Kirin, Novartis Pharma AG, Nitto Medic, Ohtsuka, Ono, Santen, and Senjyu. Dr Wong reported receiving grants and personal fees from Novartis Pharma AG during the conduct of the study; receiving grants and personal fees from Bayer Healthcare and Genentech; receiving personal fees from Roche and Samsung outside the submitted work; being a co-inventor and cofounder of Plano and EyRiS; and being a consultant for Allergan, Bayer Healthcare, Boehringer-Ingelheim, Genentech, Merck, Novartis Pharma AG, Oxurion (formerly ThromboGenics), Roche, and Samsung. Dr Chen reported receiving lecture fees from Bayer Healthcare and personal fees from Novartis Pharmaceuticals outside the submitted work. Dr Ruamviboonsuk reported receiving grants and consulting fees from Bayer Healthcare, Novartis Pharma AG, and Roche. Dr Tan reported receiving personal fees from Novartis Pharma AG during the conduct of the study; receiving nonfinancial support from Heidelberg Engineering; receiving personal fees and nonfinancial support from Bayer Healthcare and Novartis Pharma AG outside the submitted work; and receiving conference support from Allergan, Bayer, and Novartis Pharma AG. Dr Lee reported receiving consulting fees from Allergan, Bayer Healthcare, Boehringer Ingelheim, Novartis Pharma AG, Roche, and Santen outside the submitted work. Dr Cheung reported receiving grants, personal fees, and nonfinancial support from Novartis Pharma AG during the conduct of the study; receiving grants, personal fees, and nonfinancial support from Bayer Healthcare, Boehringer Ingelheim, Topcon, and Carl Zeiss; and receiving personal fees and nonfinancial support from Allergan and Roche during the conduct of the study. Dr Ngah reported receiving lecture fees from Allergan, Bayer Healthcare, and Novartis Pharma AG and receiving research grants from Novartis for the study. Dr Patalauskaite reported being an employee of Novartis Ireland Ltd during the conduct of the study. Dr Margaron reported being an employee of Novartis Pharma AG, Basel, Switzerland, during the conduct of the study. Dr Koh reported receiving consulting fees and honoraria from Alcon, Allergan, Apellis, Bayer, Boehringer Mannheim, Carl Zeiss Meditec, Heidelberg, Novartis Pharma AG, and Topcon.

Funding/Support: This trial was supported by Novartis Pharma AG.

Role of the Funder/Sponsor: In conjunction with the EVEREST II study group, Novartis Pharma AG participated in the design of the study; analysis and interpretation of the data; preparation, review, and approval of the manuscript; the decision to submit the manuscript for publication; the conduct of the study; and oversight of the collection and management of data.

Group Information: The EVEREST II Study Group members include Kanji Takahashi, MD, Kansai Medical University Hospital, Hirakata-city, Osaka, Japan; Kunihiko Shiraki, MD, Osaka City University Hospital, Osaka-city, Osaka, Japan; Yasuo Yanagi, MD, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan; Satoshi Kato, MD, PhD, The University of Tokyo Hospital, Bunkyo-ku, Tokyo, Japan; Hiroko Terasaki, MD, Nagoya University Hospital, Nagoya-city, Aichi, Japan; Masahito Ohji, MD, Shiga University of Medical Science Hospital, Ohtsu-city, Shiga, Japan; Tetsuju Sekiryu, MD, Fukushima Medical University Hospital, Fukushima-city, Fukushima, Japan; Shoji Kishi, MD, Gunma University Hospital, Maebashi-city, Gunma, Japan; Masahiro Morimoto, MD, Gunma University Hospital, Maebashi-city, Gunma, Japan; Tatsuro Ishibashi, MD, Kyushu University Hospital, Fukuoka city, Fukuoka, Japan; Yuji Oshima, MD, Kyushu University Hospital, Fukuoka city, Fukuoka, Japan; Koh Hei Sonoda, MD, Kyushu University Hospital, Fukuoka city, Fukuoka, Japan; Rvusaburo Mori, MD, Surugadai Nihon University Hospital, Kanda Surugadai, Chiyoda, Tokyo, Japan; Ayame Annabelle Okada, MD, Kyorin University Hospital, Shinkawa, Mitaka, Tokyo, Japan; Tomohiro lida, MD, Tokyo Women's Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, Japan; Takayuki Baba, MD, Chiba University Hospital, lnohana Chuo-ku Chiba-shi Chiba, Japan; Fumio Shiraga, MD, Okayama University Hospital, Shikata-cho, Kita-ku, Okayama, Okayama, Japan; Hideyasu Oh, MD, Hyogo Prefectural Amagasaki General Medical Center, Higashinaniwa-cho, Amagasaki-city, Hyogo, Japan; Toshiya Sakurai, MD, Tane Memorial Eye Hospital, Sakaigawa, Nishi-ku, Osaka, Japan; Nagako Kondo, MD, Miyake Eye Hospital, Ozone, Kita-ku, NagOya City, Japan; Shigeru Honda, MD, Kobe University Hospital, 7-5-2, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan; Mineo Kondo, MD, Mie University Hospital, 2-174, Edobashi, Tsu, Mie, Japan; Masahiro Miura, MD, Tokyo Medical University Ibaraki Medical Center, Inashiki-gun Ibaraki, Japan; Chieko Shiragami, MD, Kagawa University Hospital, Kita-gun, Kagawa Japan; Yasuo Kurimoto, MD, Kobe City Medical Center General Hospital, Kobe-city, Hyogo, Japan; Yuk Yau Timothy Lai, MD, Chinese University of Hong Kong, Hong Kong; lan Y. H. Wong, MMed, Queen Mary Hospital, Hong Kong; Wonki Lee, MD, The Catholic University of Korea Seoul, St. Mary’s Hospital, Seoul, Korea; Hakyoung Kim, MD, PhD, Kangnam Sacred Heart Hospital, Seoul, Korea; Kyu Hyung Park, MD, Seoul National University Bundang Hospital, Bundang Seongnam, Korea; Hyung-Woo Kwak, MD, PhD, Kyung Hee University Hospital, Seoul, Korea; Eung Suk Kim, MD, PhD, Kyung Hee University Hospital, Seoul, Korea; Dongwon Lee, MD, PhD, Kim's Eye Hospital, Seoul, Korea; Taegon Lee, MD, Kim's Eye Hospital, Seoul, Korea; Nikolle Tan, MMed, Tan Tock Seng Hospital, Ophthalmology, Singapore; Rajesh Rajagopalan, MBBS, Tan Tock Seng Hospital Ophthalmology, Singapore; Gemmy Cheung, MBBS, Singapore National Eye Centre, Singapore; Caroline Ka Lin Chee, MMed, National University Hospital, Singapore; Shih-Jen Chen, MD, PhD, Taipei Veterans General Hospital, Taipei, Taiwan; Chi-Chun Lai, MD, Chang Gung Memorial Hospital Linkou, Lin-Ko, Taiwan; Lee-Jen Chen, MD, MacKay Memorial Hospital, Taipei, Taiwan; Chung-May Yang, MD, National Taiwan University Hospital, Taipei, Taiwan; San-Ni Chen, MD, Changhua Christian Hospital, Changhua, Taiwan; Shwu-Jiuan Sheu, MD, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; Paisan Ruamviboonsuk, MD, Rajavithi Hospital, Bangkok, Thailand; Prut Hanutasaha, MD, Ramathibodi Hospital, Bangkok, Thailand; Patama Bhurayanontachai, MD, Songklanagarind Hospital, Songkla, Thailand; Nor Fariza Ngah, MBBS, Hospital Selayang, Batu Caves, Selangor, Malaysia; and Kenneth Choong Sian Fong, Sunway Medical Centre, Petaling Jaya Selangor Darul Ehsan, Malaysia.

Data Sharing Statement: See Supplement 3.

Additional Contributions: Steven Cartmell, PhD (Product Lifestyle Services, Novartis Ireland Ltd, Dublin, Ireland), and Shridevi Venkataramani, PhD (Scientific Services Practice, PLS, Novartis Healthcare Private Limited, Hyderabad, India), assisted with medical writing and editorial assistance toward the development of this article. Drs Cartmell and Venkataramani are employed by Novartis.

References
1.
Wong  RLM , Lai  TYY .  Polypoidal choroidal vasculopathy: an update on therapeutic approaches.   J Ophthalmic Vis Res. 2013;8(4):359-371.PubMedGoogle Scholar
2.
Laude  A , Cackett  PD , Vithana  EN ,  et al.  Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: same or different disease?   Prog Retin Eye Res. 2010;29(1):19-29. doi:10.1016/j.preteyeres.2009.10.001 PubMedGoogle ScholarCrossref
3.
Cheung  CMG , Lai  TYY , Ruamviboonsuk  P ,  et al.  Polypoidal choroidal vasculopathy: definition, pathogenesis, diagnosis, and management.   Ophthalmology. 2018;125(5):708-724. doi:10.1016/j.ophtha.2017.11.019 PubMedGoogle ScholarCrossref
4.
Honda  S , Matsumiya  W , Negi  A .  Polypoidal choroidal vasculopathy: clinical features and genetic predisposition.   Ophthalmologica. 2014;231(2):59-74. doi:10.1159/000355488 PubMedGoogle ScholarCrossref
5.
Iida  T .  Polypoidal choroidal vasculopathy with an appearance similar to classic choroidal neovascularisation on fluorescein angiography.   Br J Ophthalmol. 2007;91(9):1103-1104. doi:10.1136/bjo.2007.116160 PubMedGoogle ScholarCrossref
6.
Kokame  GT .  Polypoidal choroidal vasculopathy—an important diagnosis to make with therapeutic implications.   Retina. 2012;32(8):1446-1448. doi:10.1097/IAE.0b013e3182695bf8 PubMedGoogle ScholarCrossref
7.
Wong  CW , Yanagi  Y , Lee  W-K ,  et al.  Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians.   Prog Retin Eye Res. 2016;53:107-139. doi:10.1016/j.preteyeres.2016.04.002 PubMedGoogle ScholarCrossref
8.
Yadav  S , Parry  DG , Beare  NAV , Pearce  IA .  Polypoidal choroidal vasculopathy: a common type of neovascular age-related macular degeneration in Caucasians.   Br J Ophthalmol. 2017;101(10):1377-1380. doi:10.1136/bjophthalmol-2016-310074 PubMedGoogle ScholarCrossref
9.
Koh  AHC , Chen  L-J , Chen  S-J ,  et al; Expert PCV Panel.  Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment.   Retina. 2013;33(4):686-716. doi:10.1097/IAE.0b013e3182852446 PubMedGoogle ScholarCrossref
10.
Koh  A , Lee  WK , Chen  L-J ,  et al.  EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy.   Retina. 2012;32(8):1453-1464. doi:10.1097/IAE.0b013e31824f91e8 PubMedGoogle ScholarCrossref
11.
Koh  A , Lai  TYY , Takahashi  K ,  et al; EVEREST II study group.  Efficacy and safety of ranibizumab with or without verteporfin photodynamic therapy for polypoidal choroidal vasculopathy: a randomized clinical trial.   JAMA Ophthalmol. 2017;135(11):1206-1213. doi:10.1001/jamaophthalmol.2017.4030 PubMedGoogle ScholarCrossref
12.
Wong  CW , Cheung  CMG , Mathur  R ,  et al.  Three-year results of polypoidal choroidal vasculopathy treated with photodynamic therapy: retrospective study and systematic review.   Retina. 2015;35(8):1577-1593. doi:10.1097/IAE.0000000000000499 PubMedGoogle ScholarCrossref
13.
Lai  TYY , Chan  W-M , Liu  DTL , Luk  FOJ , Lam  DSC .  Intravitreal bevacizumab (Avastin) with or without photodynamic therapy for the treatment of polypoidal choroidal vasculopathy.   Br J Ophthalmol. 2008;92(5):661-666. doi:10.1136/bjo.2007.135103 PubMedGoogle ScholarCrossref
14.
Gomi  F , Oshima  Y , Mori  R ,  et al.  Initial versus delayed photodynamic therapy in combination with ranibizumab for treatment of polypoidal choroidal vasculopathy: the Fujisan study.   Retina. 2015;35(8):1569-1576. doi:10.1097/IAE.0000000000000526 PubMedGoogle ScholarCrossref
15.
Tang  K , Si  J-K , Guo  D-D ,  et al.  Ranibizumab alone or in combination with photodynamic therapy vs photodynamic therapy for polypoidal choroidal vasculopathy: a systematic review and meta-analysis.   Int J Ophthalmol. 2015;8(5):1056-1066.PubMedGoogle Scholar
16.
Wang  W , He  M , Zhang  X .  Combined intravitreal anti-VEGF and photodynamic therapy versus photodynamic monotherapy for polypoidal choroidal vasculopathy: a systematic review and meta-analysis of comparative studies.   PLoS One. 2014;9(10):e110667. doi:10.1371/journal.pone.0110667 PubMedGoogle Scholar
17.
World Medical Association.  World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.   JAMA. 2013;310(20):2191-2194. doi:10.1001/jama.2013.281053PubMedGoogle ScholarCrossref
18.
Tan  CS , Ngo  WK , Chen  JP , Tan  NW , Lim  TH , Group  ES ; EVEREST Study Group.  EVEREST study report 2: imaging and grading protocol, and baseline characteristics of a randomised controlled trial of polypoidal choroidal vasculopathy.   Br J Ophthalmol. 2015;99(5):624-628. doi:10.1136/bjophthalmol-2014-305674 PubMedGoogle ScholarCrossref
19.
 Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP report 1  [published correction appears in Arch Ophthalmol. 2000;118(4):488].  Arch Ophthalmol. 1999;117(10):1329-1345. doi:10.1001/archopht.117.10.1329 PubMedGoogle ScholarCrossref
20.
Bressler  NM ; Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study Group.  Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: two-year results of 2 randomized clinical trials—Tap report 2.   Arch Ophthalmol. 2001;119(2):198-207.PubMedGoogle Scholar
21.
Rosenfeld  PJ , Brown  DM , Heier  JS ,  et al; MARINA Study Group.  Ranibizumab for neovascular age-related macular degeneration.   N Engl J Med. 2006;355(14):1419-1431. doi:10.1056/NEJMoa054481 PubMedGoogle ScholarCrossref
22.
Chen  S-N , Cheng  C-K , Yeung  L ,  et al.  One-year real-world outcomes of ranibizumab 0.5 mg treatment in Taiwanese patients with polypoidal choroidal vasculopathy: a subgroup analysis of the REAL study.   Int J Ophthalmol. 2018;11(11):1802-1808.PubMedGoogle Scholar
23.
Lee  WK , Iida  T , Ogura  Y ,  et al; PLANET Investigators.  Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy in the PLANET study: a randomized clinical trial.   JAMA Ophthalmol. 2018;136(7):786-793. doi:10.1001/jamaophthalmol.2018.1804 PubMedGoogle ScholarCrossref
24.
Wong  TY , Ogura  Y , Lee  WK ,  et al; PLANET Investigators.  Efficacy and safety of intravitreal aflibercept for polypoidal choroidal vasculopathy: two-year results of the Aflibercept in Polypoidal Choroidal Vasculopathy Study.   Am J Ophthalmol. 2019;204:80-89. doi:10.1016/j.ajo.2019.02.027 PubMedGoogle ScholarCrossref
25.
Zhang  X , Lai  TYY .  Baseline predictors of visual acuity outcome in patients with wet age-related macular degeneration.   Biomed Res Int. 2018;2018:9640131. doi:10.1155/2018/9640131 PubMedGoogle Scholar
26.
Akaza  E , Yuzawa  M , Matsumoto  Y , Kashiwakura  S , Fujita  K , Mori  R .  Role of photodynamic therapy in polypoidal choroidal vasculopathy.   Jpn J Ophthalmol. 2007;51(4):270-277. doi:10.1007/s10384-007-0452-3 PubMedGoogle ScholarCrossref
27.
Verteporfin In Photodynamic Therapy Study Group.  Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization—verteporfin in photodynamic therapy report 2.   Am J Ophthalmol. 2001;131(5):541-560. doi:10.1016/S0002-9394(01)00967-9 PubMedGoogle ScholarCrossref
28.
Tan  CS , Ngo  WK , Lim  LW , Tan  NW , Lim  TH , Group  ES ; EVEREST Study Group.  EVEREST study report 3: diagnostic challenges of polypoidal choroidal vasculopathy: lessons learnt from screening failures in the EVEREST study.   Graefes Arch Clin Exp Ophthalmol. 2016;254(10):1923-1930. doi:10.1007/s00417-016-3333-y PubMedGoogle ScholarCrossref
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