Efficacy and Safety of Intravitreal Aflibercept Treat and Extend for Polypoidal Choroidal Vasculopathy in the ATLANTIC Study: A Randomized Clinical Trial.

IMPORTANCE: Polypoidal choroidal vasculopathy (PCV) is far less common and studied in a Caucasian population than in an Asian population, and the optimal treatment approach remains to be confirmed. METHODS: A 52-week, double-masked, sham-controlled, phase 4, investigator-initiated randomized clinical trial (RCT) in naive symptomatic Caucasian patients with PCV treated with aflibercept in a treat-and-extend regimen (T&E) (intravitreal aflibercept injection [IVAI] T&E). Patients were randomized at week 16 to receive IVAI T&E plus either sham photodynamic therapy (PDT) or standard fluence PDT with verteporfin. The main outcome measures were changes in best-corrected visual acuity (BCVA) from baseline to 52 weeks and polyp occlusion at week 52. Data are presented as median (interquartile range [IQR]) for BCVA, number of IVAI, and change in central retinal thickness (CRT). RESULTS: Of the 50 patients included in the study, 48 patients completed the 52 weeks of follow-up. During this period, a significant median (IQR) BCVA gain of 6 [2-12] Early Treatment Diabetic Retinopathy Study letters was observed for all patients (p < 0.001), after 8 (7-9) injections, with a significant reduction of -93.0 [-154.0, -44.0] µm in central macular thickness (p < 0.001). Using indocyanine green angiography, a complete occlusion of polypoidal lesions was documented in 72% of the cases. Still, no significant difference was detected between the sham PDT and the aflibercept PDT arms, at week 52, for BCVA change (6.5 [2-11] vs. 5 [2-13] letters (p = 0.98)), number of IVAIs (8.5 [7-9] vs. 8 [7-9] (p = 0.21)), change in CRT (-143 [-184; -47] vs. -89 [-123; -41.5] µm [p = 0.23]), and rates of complete polyp occlusion: 77 versus 68% (p = 0.53) or presence of fluid: 68 versus 57% (p = 0.56). No serious ocular adverse events were registered in the 2 arms. CONCLUSIONS AND RELEVANCE: To our knowledge, this is the first RCT to compare aflibercept T&E monotherapy with aflibercept T&E plus verteporfin PDT in a Caucasian population with PCV. Aflibercept monotherapy in a T&E showed to be effective and safe with a significant median BCVA improvement of 6 letters and a complete occlusion of polypoidal lesions in near 3 quarters of the eyes, at 1 year. As only 22% of the eyes underwent PDT treatment, the benefit of combined treatment for PCV in Caucasian patients could not be definitively elucidated from this study. TRIAL REGISTRATION: The clinical trial was registered in ClinicalTrials.gov Identifier NCT02495181 and the European Union Drug Regulating Authorities Clinical Trials Database EudraCT No. 2015-001368-20.

Polypoidal Choroidal Vasculopathy in Caucasians: Morphological Findings from Multimodal Retinal Imaging.

PURPOSE: The aim of the study was to characterize the morphological features of polypoidal choroidal vasculopathy (PCV) in a large Caucasian population. METHODS: We conducteda multicenter, cross-sectional study of treatment-naïve patients with PCV. Baseline fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) were assessed by trained medical graders. Typical PCV features were explored, and retinal thickness (RT) and choroidal thickness (CT) measurements were performed. RESULTS: Seventy-nine eyes of 73 patients (mean age, 72.6 ± 11.9 years) were included. ICGA identified macular polyps in 89.9% of cases. SD-OCT revealed mostly subretinal fluid (93.6%) and a retinal pigment epithelium (RPE) detachment in 91.4%, with sharp protrusion in 67.0% of cases. Polyp-like structures were seen in 74.3% of cases, mostly adherent to an elevated RPE (69.6%). Type 1 neovascularization (NV) was identified in 74.7% of patients, while 16.5% had a mixed NV. The mean macular CT was 220.9 ± 83.2 µm (range, 67.9-403.6). Diffuse and focal pachychoroid were observed in 26.6 and 30.4% of patients, respectively. Soft drusen were reported in 62.0% of cases, but retinal hemorrhage occurred in only 19.0% of cases. CONCLUSION: The morphological features of PCV in Caucasians are similar to those reported in Asians. Pachychoroid signs were found in nearly half of our cohort. However, the mean age at presentation, high prevalence of soft drusen, and low prevalence of large subretinal hemorrhages make PCV closer to age-related macular degeneration in this ethnic group.

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future.

PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. DESIGN: Meta-analysis of prevalence data. PARTICIPANTS: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. METHODS: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). MAIN OUTCOME MEASURES: Prevalence of early and late AMD, BCVA, and number of AMD cases. RESULTS: Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%-5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged ≥85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer ≥80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. CONCLUSION: We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

Progression of myopic maculopathy after treatment of choroidal neovascularization.

PURPOSE: To evaluate the long-term progression of myopic maculopathy and functional outcome after treatment of myopic choroidal neovascularization (CNV) with photodynamic therapy (PDT) and/or intravitreal ranibizumab (IVR). METHODS: Retrospective study with a cross-sectional evaluation. Eyes were assigned to 4 groups (PDT, IVR, PDT + IVR, dry myopic maculopathy) and evaluated with best-corrected visual acuity, color fundus photography and spectral-domain optical coherence tomography. Chorioretinal atrophy progression was quantified. RESULTS: Fifty-four eyes were included with a mean follow-up of 80.6 ± 28.0 months. The prevalence of diffuse, patchy and macular atrophy increased during the follow-up, in contrast with tessellated fundus, lacquer cracks and active CNV. Progression of macular atrophy was significant in the 3 treatment groups (p < 0.05) and predictive of visual acuity. It depended on age, degree of myopia and presence of staphyloma, but not on the type of treatment. CONCLUSIONS: The long-term functional outcome of eyes with myopic CNV is more dependent on the progression of macular atrophy, and not on the type of treatment.

Photodynamic therapy for chronic central serous chorioretinopathy: a 4-year follow-up study.

PURPOSE: To evaluate the efficacy and safety of standard photodynamic therapy with verteporfin at 48 months in patients with chronic central serous chorioretinopathy. METHODS: A retrospective, multicenter, interventional case series analysis in patients with chronic central serous chorioretinopathy, treated with standard photodynamic therapy, and with ≥4 years of follow-up. Evaluations were performed every 3 months in the first year, every 6 months in the second year, and thereafter annually. Optical coherence tomography was performed in all visits. Fluorescein angiography and indocyanine green angiography were performed at baseline and thereafter as necessary. Retinal thickness on optical coherence tomography was measured manually, evaluating central macular thickness and neural retina thickness. Main outcomes included the evolution of best-corrected visual acuity, the resolution of subretinal fluid, documented with optical coherence tomography, the number of treatments, and the evaluation of neural retina thickness during the 48 months of follow-up. RESULTS: The study included 46 eyes of 42 patients, 38 men (90.4%) and 4 women (9.5%), with mean age of 49.19 ± 9.9 years (range, 32-70 years), and the minimal follow-up period was 48 months (mean, 56.8 ±10.3 months). Subretinal fluid was observed in all the included eyes at baseline, and 10 eyes (21.7%) had intraretinal diffuse or cystoid fluid. Concerning the mean best-corrected visual acuity, a statistically significant improvement (P < 0.01, Student t-test) was registered from 58.8 ± 18.3 letters at baseline to 66.9 ± 18.6 letters at 48th month. A complete resolution of subretinal fluid was achieved in 93.4%, and resolution of intraretinal fluid occurred in all 10 cases at 48 months. Neural retina thickness remained stable during the 48 months of follow-up (163.8 ± 47 µm at baseline and 163.8 ± 46 µm at 48 months). The mean number of treatments was 1.08 ± 0.3. No systemic or ocular side effects were registered. CONCLUSION: Standard photodynamic therapy with verteporfin was effective and safe in chronic central serous chorioretinopathy treatment with a significant improvement in the long term, both anatomic and visual, without inducing additional retinal atrophy or systemic adverse effects.

Photodynamic therapy in highly myopic eyes with choroidal neovascularization: 5 years of follow-up.

PURPOSE: To evaluate the long-term safety and efficacy of photodynamic therapy in the treatment of choroidal neovascularization associated with pathologic myopia. METHODS: Five-year retrospective study of 43 consecutive eyes of 36 patients with juxtafoveal or subfoveal choroidal neovascularization and pathologic myopia treated with photodynamic therapy. RESULTS: Mean best-corrected visual acuity changed from 20/125 +1 letter (0.78 logarithm of the minimum angle of resolution) at baseline to 20/100 (0.70 logarithm of the minimum angle of resolution) at 5 years (P = 0.122). Final best-corrected visual acuity improved in 53.5% of the eyes, remained stable in 11.6%, and decreased in 34.9%. A visual acuity gain of ≥3 lines occurred in 32.6% of the eyes, and a visual acuity decrease of ≥3 lines was registered in 20.9% of the cases at 5 years. Only patient's age and initial visual acuity showed to have a significant predictive value for the final visual acuity outcome (P = 0.024 and P = 0.002, respectively). CONCLUSION: Photodynamic therapy with verteporfin may increase the chance of stabilizing and improving vision in patients with choroidal neovascularization from pathologic myopia at 5 years. Better results were found in younger patients (<55 years).

Choroidal thickness after treatment for myopic choroidal neovascularization.

PURPOSE: To evaluate choroidal thickness in highly myopic eyes with choroidal neovascularization (CNV), 3 or more years after treatment with photodynamic therapy (PDT), intravitreal ranibizumab (IVR), or both (PDT + IVR). METHODS: The medical records of patients with high myopia and CNV treated with PDT or IVR in our department were reviewed. Eyes meeting the inclusion criteria were assigned to 3 groups: PDT, IVR, and PDT + IVR. A fourth group, "dry myopic maculopathy," included the contralateral highly myopic eyes that never developed CNV. All patients performed a cross-sectional evaluation with best-corrected visual acuity (BCVA), measurement of axial length, color fundus photography, and enhanced depth imaging with spectral domain optical coherence tomography. RESULTS: Forty-two eyes (21 patients) were included: 11 eyes (26.2%) in the PDT group, 8 (19.0%) in the IVR group, 9 (21.4%) in the PDT + IVR group, and 14 (33.3%) in the dry maculopathy group. Subfoveal choroidal thickness showed no significant differences between groups (p>0.05). Positive correlation was found between BCVA and macular choroidal thickness (r = +0.293, p<0.001). Regression analysis showed that age (p<0.001), axial length (p<0.001), sex (p = 0.001), and myopic lesions such as tessellated fundus (p = 0.046) and patchy atrophy (p = 0.008) were predictive of choroidal thickness. Type of treatment was not predictive of choroidal thickness. CONCLUSIONS: Older age and greater axial length are the major factors associated with macular choroidal thinning in highly myopic eyes submitted to CNV treatment. The type of treatment performed for myopic CNV had no predictive contribution for choroidal thickness.