PMID- 29801063 OWN - NLM STAT- MEDLINE DCOM- 20190927 LR - 20220408 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 136 IP - 7 DP - 2018 Jul 1 TI - Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial. PG - 786-793 LID - 10.1001/jamaophthalmol.2018.1804 [doi] AB - IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is common in Asian populations, but an optimal treatment approach remains to be confirmed. OBJECTIVE: To evaluate intravitreal aflibercept injection (IAI) in participants with PCV and compare IAI monotherapy with IAI plus rescue photodynamic therapy (PDT). DESIGN, SETTING, AND PARTICIPANTS: This 96-week, double-masked, sham-controlled phase 3b/4 randomized clinical trial was conducted at multiple centers in Australia, Germany, Hong Kong, Hungary, Japan, Singapore, South Korea, and Taiwan from May 2014 to August 2016, and included adults 50 years or older with symptomatic macular PCV and a best-corrected visual acuity of 73 to 24 Early Treatment Diabetic Retinopathy Study letters (20/40-20/320 Snellen equivalent). INTERVENTIONS: Participants received 2 mg of IAI at weeks 0, 4, and 8. At week 12, participants with a suboptimal response were randomized 1:1 to receive IAI plus sham PDT (IAI monotherapy) or a "rescue" of IAI plus rescue PDT (IAI/PDT). Participants who did not qualify for rescue received IAI every 8 weeks; those qualifying for rescue received IAI every 4 weeks plus sham/active PDT. When the rescue criteria were no longer met, injection intervals were gradually extended to 8 weeks. MAIN OUTCOMES AND MEASURES: Noninferiority of IAI monotherapy to IAI/PDT for mean change in best-corrected visual acuity from baseline to week 52 (95% CI of the difference entirely above -5 letters). RESULTS: Of the 318 participants, the mean (SD) age was 70.6 (8.2) years, 96 (30.2%) were women, and 152 (47.8%) were Japanese. Monotherapy with IAI was noninferior to IAI/PDT for the primary end point (+10.7 vs +10.8 letters, respectively; 95% CI, -2.9 to 1.6; P = .55), with few participants requiring rescue therapy (19 [12.1%] vs 23 [14.3%], respectively). Participants in both treatment groups had similar reductions in central subfield thickness from baseline to week 52 (-137.7 [IAI monotherapy] vs -143.5 mum [IAI/PDT]). At week 52, 49 (38.9%) and 60 participants (44.8%) had no polypoidal lesions observed on indocyanine green angiography in the IAI monotherapy and IAI/PDT groups, respectively. Furthermore, 116 (81.7%) and 136 (88.9%), respectively, had no polypoidal lesions with leakage. The most frequent ocular adverse events were conjunctival hemorrhage (IAI monotherapy, 8 [5.1%]) and dry eye (IAI/PDT, 9 [5.6%]). CONCLUSIONS AND RELEVANCE: Improvement in visual and/or functional outcomes was achieved in more than 85% of participants who were treated with IAI monotherapy, with no signs of leakage from polypoidal lesions in more than 80%. As fewer than 15% met the criteria of a suboptimal response to receive PDT, the potential benefit of adding PDT cannot be determined. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02120950. FAU - Lee, Won Ki AU - Lee WK AD - Department of Ophthalmology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea. FAU - Iida, Tomohiro AU - Iida T AD - Department of Ophthalmology, Tokyo Women's Medical University, Tokyo, Japan. FAU - Ogura, Yuichiro AU - Ogura Y AD - Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan. FAU - Chen, Shih-Jen AU - Chen SJ AD - Department of Ophthalmology, Taipei Veterans General Hospital, School of Medicine, National Yang-Ming University Taipei, Taiwan. FAU - Wong, Tien Yin AU - Wong TY AD - Singapore Eye Research Institute and National Eye Centre, Singapore. AD - Duke-NUS Medical School, National University of Singapore, Singapore. FAU - Mitchell, Paul AU - Mitchell P AD - University of Sydney, Sydney, Australia (Westmead Institute for Medical Research). FAU - Cheung, Gemmy Chui Ming AU - Cheung GCM AD - Singapore Eye Research Institute and National Eye Centre, Singapore. AD - Duke-NUS Medical School, National University of Singapore, Singapore. FAU - Zhang, Zhongqi AU - Zhang Z AD - Bayer Pharmaceuticals, Berlin, Germany. FAU - Leal, Sergio AU - Leal S AD - Bayer Pharmaceuticals, Berlin, Germany. FAU - Ishibashi, Tatsuro AU - Ishibashi T AD - Department of Ophthalmology, Kyushu University Hospital, Fukuoka, Japan. CN - PLANET Investigators LA - eng SI - ClinicalTrials.gov/NCT02120950 PT - Clinical Trial, Phase III PT - Clinical Trial, Phase IV PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Ophthalmol JT - JAMA ophthalmology JID - 101589539 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Photosensitizing Agents) RN - 0 (Recombinant Fusion Proteins) RN - 0 (VEGFA protein, human) RN - 0 (Vascular Endothelial Growth Factor A) RN - 15C2VL427D (aflibercept) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) SB - IM CIN - JAMA Ophthalmol. 2018 Jul 1;136(7):794-795. PMID: 29801084 EIN - JAMA Ophthalmol. 2018 Jul 1;136(7):840. PMID: 29902303 MH - Aged MH - Angiogenesis Inhibitors/adverse effects/*therapeutic use MH - Choroid/blood supply MH - Choroidal Neovascularization/diagnostic imaging/*drug therapy/physiopathology MH - Double-Blind Method MH - Female MH - Fundus Oculi MH - Humans MH - Intravitreal Injections MH - Male MH - Middle Aged MH - Photochemotherapy MH - Photosensitizing Agents/therapeutic use MH - Polyps/diagnostic imaging/*drug therapy/physiopathology MH - Receptors, Vascular Endothelial Growth Factor/*therapeutic use MH - Recombinant Fusion Proteins/adverse effects/*therapeutic use MH - Tomography, Optical Coherence MH - Treatment Outcome MH - Vascular Endothelial Growth Factor A/antagonists & inhibitors MH - Visual Acuity/physiology PMC - PMC6136040 COIS- Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee reports receiving personal fees and nonfinancial support from Bayer during the conduct of the study and personal fees from Bayer, Novartis, Allergan, and Santen outside the submitted work. Dr Iida reports receiving personal fees from Bayer during the conduct of the study; grants and personal fees from Alcon, AMO Japan, Bayer, Novartis, Otsuka Pharmaceutical, Santen Pharmaceutical, Senju Pharmaceutical, and Wakamoto Pharmaceutical; grants from Canon, Hoya, Kowa, Nidek, and Pfizer; and personal fees from Bayer and Chugai Pharmaceutical outside the submitted work. Prof Ogura reports receiving personal fees from Bayer during the conduct of the study and personal fees from Bayer, Alcon, Bausch and Lomb, Janssen Pharma, Kissei Pharma, Kowa, Novartis, Santen, Sanwa Kagaku, Senju, Topcon, and Wakamoto outside the submitted work. Dr Chen reports receiving personal fees and nonfinancial support from Bayer, Novartis, and Allergan and personal fees from Medical Integrating System during the conduct of the study. Dr Wong reports receiving consultancy fees and payments for lectures from Abbott, Allergan, Bayer, and Novartis outside the submitted work. Dr Mitchell reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Dr Cheung reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. Drs Zhang and Leal are employees of Bayer Pharmaceuticals. Dr Ishibashi reports receiving consulting fees from Bayer during the conduct of this study and outside the submitted work. EDAT- 2018/05/26 06:00 MHDA- 2019/09/29 06:00 PMCR- 2018/05/02 CRDT- 2018/05/26 06:00 PHST- 2018/05/26 06:00 [pubmed] PHST- 2019/09/29 06:00 [medline] PHST- 2018/05/26 06:00 [entrez] PHST- 2018/05/02 00:00 [pmc-release] AID - 2680578 [pii] AID - eoi180036 [pii] AID - 10.1001/jamaophthalmol.2018.1804 [doi] PST - ppublish SO - JAMA Ophthalmol. 2018 Jul 1;136(7):786-793. doi: 10.1001/jamaophthalmol.2018.1804.