PMID- 28983556 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20220408 IS - 2168-6173 (Electronic) IS - 2168-6165 (Print) IS - 2168-6165 (Linking) VI - 135 IP - 11 DP - 2017 Nov 1 TI - Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial. PG - 1206-1213 LID - 10.1001/jamaophthalmol.2017.4030 [doi] AB - IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is a common subtype of exudative age-related macular degeneration among Asian individuals. To our knowledge, there are no large randomized clinical trials to evaluate intravitreal ranibizumab, with and without verteporfin photodynamic therapy (vPDT), for the treatment of PCV. OBJECTIVE: To compare the efficacy and safety of combination therapy of ranibizumab and vPDT with ranibizumab monotherapy in PCV. DESIGN, SETTING, AND PARTICIPANTS: A double-masked, multicenter randomized clinical trial of 322 Asian participants with symptomatic macular PCV confirmed by the Central Reading Center using indocyanine green angiography was conducted between August 7, 2013, and March 2, 2017. INTERVENTIONS: Participants were randomized 1:1 to ranibizumab, 0.5 mg, and vPDT (n = 168; combination therapy group) or ranibizumab, 0.5 mg, and sham PDT (n = 154; monotherapy group). All participants received 3 consecutive monthly ranibizumab injections, followed by a pro re nata regimen. Participants also received vPDT/sham PDT on day 1, followed by a pro re nata regimen based on the presence of active polypoidal lesions. MAIN OUTCOMES AND MEASURES: Step 1 assessed whether combination therapy was noninferior (5-letter margin) to monotherapy for change in best-corrected visual acuity from baseline and superior in complete polyp regression. If noninferiority was established, step 2 assessed whether combination therapy was superior to monotherapy measured by best-corrected visual acuity change at month 12. RESULTS: Baseline demographics of the 322 participants were comparable between the treatment groups. Mean (SD) age of the patients was 68.1 (8.8) years, and overall, 69.9% of the patients were men. At baseline, the overall mean best-corrected visual acuity and mean central subfield thickness were 61.1 letters and 413.3 mum, respectively. At 12 months, mean improvement from baseline was 8.3 letters with combination therapy vs 5.1 letters with monotherapy (mean difference, 3.2 letters; 95% CI, 0.4-6.1), indicating that combination therapy met the predefined criterion for noninferiority as well as being superior to monotherapy (P = .01). Combination therapy was also superior to monotherapy in achieving complete polyp regression at month 12 (69.3% vs 34.7%; P < .001). Over 12 months, the combination therapy group received a median of 4.0 ranibizumab injections compared with 7.0 in the monotherapy group. Vitreous hemorrhage was the only ocular serious adverse event (combination therapy group, 1 [0.6%]; monotherapy group, 3 [2.0%]). CONCLUSIONS AND RELEVANCE: After 12 months, combination therapy of ranibizumab plus vPDT was not only noninferior but also superior to ranibizumab monotherapy in best-corrected visual acuity and superior in complete polyp regression while requiring fewer injections. Combination therapy should be considered for eyes with PCV. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01846273. FAU - Koh, Adrian AU - Koh A AD - Eye and Retina Surgeons, Camden Medical Centre, Singapore, Singapore. FAU - Lai, Timothy Y Y AU - Lai TYY AD - Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China. FAU - Takahashi, Kanji AU - Takahashi K AD - Department of Ophthalmology, Kansai Medical University, Hirakata Hospital, Osaka, Japan. FAU - Wong, Tien Y AU - Wong TY AD - Singapore Eye Research Institute, Singapore National Eye Centre, Duke-NUS Medical School, National University of Singapore, Singapore. FAU - Chen, Lee-Jen AU - Chen LJ AD - Department of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan. FAU - Ruamviboonsuk, Paisan AU - Ruamviboonsuk P AD - Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand. FAU - Tan, Colin S AU - Tan CS AD - Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore. AD - National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore. FAU - Feller, Chrystel AU - Feller C AD - Novartis Pharma AG, Basel, Switzerland. FAU - Margaron, Philippe AU - Margaron P AD - Novartis Pharma AG, Basel, Switzerland. FAU - Lim, Tock H AU - Lim TH AD - Fundus Image Reading Centre, National Healthcare Group Eye Institute, Singapore. AD - National Healthcare Group Eye Institute, Tan Tock Seng Hospital, Singapore. FAU - Lee, Won Ki AU - Lee WK AD - Department of Ophthalmology, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea. CN - EVEREST II study group LA - eng SI - ClinicalTrials.gov/NCT01846273 PT - Clinical Trial, Phase IV 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 (Porphyrins) RN - 0X9PA28K43 (Verteporfin) RN - ZL1R02VT79 (Ranibizumab) SB - IM CIN - JAMA Ophthalmol. 2017 Nov 1;135(11):1214-1215. PMID: 28983554 MH - Aged MH - Aged, 80 and over MH - Angiogenesis Inhibitors/administration & dosage MH - Choroid/*blood supply/pathology MH - Choroid Diseases/diagnosis/*drug therapy MH - Double-Blind Method MH - Drug Therapy, Combination MH - Female MH - Fluorescein Angiography MH - Follow-Up Studies MH - Fundus Oculi MH - Humans MH - Injections, Intravenous MH - Intravitreal Injections MH - Male MH - Middle Aged MH - Photochemotherapy/*methods MH - Photosensitizing Agents/administration & dosage MH - Polyps/diagnosis/*drug therapy MH - Porphyrins/*administration & dosage MH - Ranibizumab/*administration & dosage MH - Retrospective Studies MH - Treatment Outcome MH - Verteporfin PMC - PMC5710379 COIS- Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Koh is a consultant for Novartis, Allergan, Carl Zeiss, Meditec, and Heidelberg Engineering. Dr Lai is a consultant for Allergan, Bayer, Novartis, and Genentech. Dr Takahashi is a consultant for Bayer and Novartis. Dr Wong received travel grants, writing/reviewing fees, and consultancy fees from Novartis and Bayer during the conduct of the study and consultancy fees from Abbott, Allergan, Genentech, Roche, and Pfizer outside the submitted work. Dr Chen receives financial support from Novartis and Bayer and is a consultant for Bayer. Dr Ruamviboonsuk is a consultant for Allergan, Bayer, and Novartis. Dr Tan receives conference support from Bayer, Heidelberg Engineering, and Novartis. Ms Feller and Dr Margaron are employees of Novartis Pharma AG, Basel, Switzerland. Dr Lim receives travel support from Heidelberg Engineering and Novartis. Dr Lee is a consultant for Alcon, Allergan, Bayer, Novartis, and Santen and is a trustee/board member for Alcon, Allergan, Bayer, and Novartis. No other disclosures were reported EDAT- 2017/10/07 06:00 MHDA- 2017/11/29 06:00 PMCR- 2017/11/09 CRDT- 2017/10/07 06:00 PHST- 2017/10/07 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/10/07 06:00 [entrez] PHST- 2017/11/09 00:00 [pmc-release] AID - 2656454 [pii] AID - eoi170083 [pii] AID - 10.1001/jamaophthalmol.2017.4030 [doi] PST - ppublish SO - JAMA Ophthalmol. 2017 Nov 1;135(11):1206-1213. doi: 10.1001/jamaophthalmol.2017.4030.