Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy

Abstract

for the EVEREST II study group 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 PARTICIPANTSA 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 MEASURESStep 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 μm, 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.

Aflibercept Treatment in Polypoidal Choroidal Vasculopathy: Results of a Prospective Study in a Caucasian Population

“…The improvement of 13 letters at 28 weeks in our study is at least comparable with the results of the VIEW 1 and 2 studies that demonstrated respective improvement of 7.8 and 8.9 letters in AMD [16]. These results are also comparable with those of combination therapy (ranibizumab + PDT) in the EVEREST and EVEREST II studies at 12 months (+10.9 and +8.3 letters, respectively) [12, 13]. On the other hand, ranibizumab monotherapy only demonstrated a 5-letter improvement in the LAPTOP study [10].…”

“…The Everest study showed that PDT alone or in combination with ranibizumab intravitreal injections (IVT) were both superior to sole ranibizumab therapy in achieving complete polyp regression (in 71.4, 77.8, and 28.6% of eyes, respectively) after 6 months of follow up [12]. The Everest study II confirmed that PDT in combination with ranibizumab IVT were superior to sole ranibizumab therapy in achieving complete polyp regression (69.3 vs. 34.7% of all eyes) after 12 months of follow-up [13]. However, complications may occur with PDT, including subretinal hemorrhage, retinal pigment epithelial (RPE) tears, and choroidal infarcts [14].…”

Five-year visual outcomes after anti-VEGF therapy with or without photodynamic therapy for polypoidal choroidal vasculopathy

“…21 The EVEREST II study reported that combination therapy was superior to IVR monotherapy in terms of the 12-month visual outcomes and number of injections. 10 Thus, data regarding the long-term outcomes of these regimens are desirable.…”

“…Further, the prospective, randomised, doublemasked, multicentre EVEREST II study showed that the 12-month VA was better for patients who received combination therapy of ranibizumab with PDT than for those who received ranibizumab alone. 10 However, the invasive effect of PDT on the retina and choroid remains concerning. 11 In clinical settings, anti-VEGF agents are often administered for PCV on a pro re nata (PRN) basis, with or without PDT.…”

Spectral-Domain Optical Coherence Tomography Angiography for the Diagnosis and Evaluation of Polypoidal Choroidal Vasculopathy

“…Once PCV is diagnosed, combination therapy with photodynamic therapy (PDT) and intravitreal anti-VEGF injections may have a higher chance of improving vision and promoting regression of polyps, DOI: 10.1159/000481540 edema, and subretinal fluid while decreasing the number of intravitreal injections needed and overall treatment burden for these patients [10,11]. Due to this importance, PCV is becoming increasingly recognized in the world, not only in Asia, where PCV can occur in up to 50% of AMD patients [12][13][14], but also in Caucasian individuals, where the prevalence of PCV in eyes with exudative AMD can reach almost a quarter [15,16].…”