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Purpose To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti–vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD). Design Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial. Participants Four hundred forty-nine patients with treatment-naive nAMD. Methods Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks. Main Outcome Measures The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks. Results No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group. Conclusions In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.

To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti-vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD).Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial.Four hundred forty-nine patients with treatment-naïve nAMD.Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks.The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks.No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group.In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.

Purpose: To describe novel cystic structures (‘outer retinal cysts’ or ORC) found in the outer retina in age-related macular degeneration (AMD). Methods: One hundred and seventy-three consecutive eyes of 88 AMD patients were prospectively examined with spectral domain optical coherence tomography (SD-OCT). The prevalence of ORCs was searched, and their sizes and shapes were determined. Results: SD-OCT revealed round or ovoid, intraretinal, hyporeflective cystic structures with a hyperreflective border in 60 eyes (56%) with neovascular AMD and in six eyes (21%) with atrophic AMD. These cystic structures were of different sizes and shapes. They remained stable in all the patients after a follow-up period of 6 months. Conclusions: Outer retinal cyst is a new type of cystic structure recently identified in AMD patients. ORCs should not be confused with intraretinal exudates or cystoid cavities and therefore do not require any treatment. The histopathological nature of ORC remains to be determined. Further studies are necessary to determine their true origin.

Purpose: To determine the sensitivity of the combination of optical coherence tomography angiography (OCTA) and structural optical coherence tomography (OCT) for detecting type 1 neovascularization (NV) and to determine significant factors that preclude visualization of type 1 NV using OCTA. Methods: Multicenter, retrospective cohort study of 115 eyes from 100 patients with type 1 NV. A retrospective review of fluorescein (FA), OCT, and OCTA imaging was performed on a consecutive series of eyes with type 1 NV from five institutions. Unmasked graders utilized FA and structural OCT data to determine the diagnosis of type 1 NV. Masked graders evaluated FA data alone, en face OCTA data alone and combined en face OCTA and structural OCT data to determine the presence of type 1 NV. Sensitivity analyses were performed using combined FA and OCT data as the reference standard. Results: A total of 105 eyes were diagnosed with type 1 NV using the reference. Of these, 90 (85.7%) could be detected using en face OCTA and structural OCT. The sensitivities of FA data alone and en face OCTA data alone for visualizing type 1 NV were the same (66.7%). Significant factors that precluded visualization of NV using en face OCTA included the height of pigment epithelial detachment, low signal strength, and treatment-naïve disease (P < 0.05, respectively). Conclusions: En face OCTA and structural OCT showed better detection of type 1 NV than either FA alone or en face OCTA alone. Combining en face OCTA and structural OCT information may therefore be a useful way to noninvasively diagnose and monitor the treatment of type 1 NV., LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, Macula Foundation, Inc.

Purpose To describe optical coherence tomographic (OCT) angiography findings in chronic central serous chorioretinopathy (CSC), and to characterize their OCT B-scans by means of the split-spectrum amplitude-decorrelation angiography algorithm. Design Evaluation of an imaging technique in a cohort of patients. Methods Fluorescein (FA) and indocyanine green (ICGA) angiography (Heidelberg Spectralis, Heidelberg, Germany), OCT angiography, and OCT angiography with the split-spectrum amplitude-decorrelation angiography algorithm (XR Optovue, Fremont, California, USA) were performed. A qualitative analysis of the entire imaging data was done. Results Twelve eyes of 10 patients were included. Mean visual acuity was 20/30. All eyes presented findings consistent with chronic CSC (lasting more than 6 months) on biomicroscopic examination, autofluorescence, FA, ICGA, and OCT. ICGA showed the characteristic choroidal hyperpermeability, while there was no evidence of choroidal neovascularization (CNV). OCT B-scans showed 2 distinct profiles of the retinal pigment epithelium (RPE): a slight RPE detachment with small undulations was evident in 7 of 12 eyes, while 5 eyes presented a flat RPE profile. OCT angiography in 7 eyes (58%) revealed the presence of a distinct CNV corresponding to the ICGA hyperpermeability. The qualitative analysis of the OCT B-scans compared to the OCT angiographic images demonstrated that the CNV corresponded to the small undulations within the slight RPE detachment, confirming its vascularized nature. On the contrary, OCT angiography showed a normal choroidal circulation in the remaining 5 eyes (42%) with a flat RPE profile. Conclusions OCT angiography allows detection of CNV in chronic CSC not visible with other imaging techniques. CNV corresponds to the small undulating RPE detachment on B-scan. This might allow an appropriate treatment resulting in a better visual outcome.

Purpose To describe polypoidal choroidal vasculopathy as a complication of tilted disk syndrome and high myopia with staphyloma. Design Retrospective interventional case series. Methods This report was a multicenter evaluation of six patients (eight eyes) with tilted disk syndrome or high myopia that was complicated by posterior staphyloma. Complete ophthalmic examination that included fluorescein angiography, optical coherence tomography (OCT), and indocyanine green angiography (ICG-A) was performed in all patients. Results All patients had macular abnormalities and visual loss. Fundus examination and fluorescein angiography showed typical features of tilted disk syndrome (five patients; six eyes) or high myopia (one patient; two eyes) with staphyloma that was associated with polypoidal choroidal vasculopathy. OCT and ICG-A confirmed the presence of polypoidal dilations in the choroid. Seven eyes were treated with laser photocoagulation or verteporfin-photodynamic therapy (V-PDT), although one eye did not require treatment. Visual acuity at the final visit had improved in three eyes, deteriorated in three eyes, and remained unchanged in two eyes. Conclusion Polypoidal choroidal vasculopathy is a potential cause of visual loss in tilted disk syndrome and high myopia. We postulate that choroidal abnormalities at the border of staphylomas induce blood-flow disturbances that are similar to those disturbances that are observed in chronic central serous chorioretinopathy, which is another condition that occasionally is associated with polypoidal choroidal vasculopathy. The pathogenesis remains unclear, and further study is required to better understand the formation of choroidal polypoidal dilations in these conditions.

Purpose: Optical coherence tomography angiography is a novel and noninvasive technique for imaging retinal microvasculature by detecting changes in reflectivity that is related to blood flow. The purpose of this study was to describe Type 2 neovascularization characteristics in age-related macular degeneration using optical coherence tomography angiography. Methods: Fourteen eyes of 14 consecutive patients with Type 2 neovascularization were prospectively included. All patients underwent a complete ophthalmological examination, including color and infrared fundus photography, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography angiography, and optical coherence tomography angiography. Results: In all cases, Type 2 lesions could be detected by optical coherence tomography angiography, presenting as a hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape (10/14), surrounded by a dark halo. The superficial layer and the deep retina showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to continue deep into the choroidal layers. Conclusion: Optical coherence tomography angiography may be a new imaging method for the diagnosis of Type 2 neovascularization in clinical routine. However, the specificity of the features needs to be investigated in further studies.