The long-term effects of anti-vascular endothelial growth factor therapy on the optical coherence tomography angiographic appearance of neovascularization in age-related macular degeneration.

BACKGROUND: The short-term effects of anti-vascular endothelial growth factor (anti-VEGF) treatment on macular neovascularization (MNV) morphology is well described, but long-term studies on morphologic changes and correlation of such changes to the type of MNV have not been conducted. This study aims to determine if different types of MNVs in neovascular AMD (nAMD) behave differently with anti-VEGF treatment as visualized on optical coherence tomography angiography (OCTA). METHODS: Treatment-naïve nAMD patients were retrospectively screened for baseline and follow-up OCTA imaging 10 or more months after initial treatment. Images were graded for MNV type, area, activity, mature versus immature vessels, vessel density, presence of atrophy, atrophy location and area. Growth rate was calculated as the percent change in lesion area from baseline over the years of follow-up. In addition, the occurrence of complete regression and the percent of lesions that grew, remained stable, and shrunk per type was also evaluated. RESULTS: Forty-three eyes from 43 patients with a mean follow-up of 2 years were evaluated. On structural OCT, 26 lesions were classified as pure type 1 MNVs, 12 MNVs had a type 2 component, and 5 MNVs had a type 3 component. Of these cases, 2 mixed-type MNVs were considered to have completely regressed. There was no significant differences in MNV area and growth rate between type 1 and type 2 lesions, but all cases of type 3 lesions shrunk in the follow-up period. There was no correlation between the number of injections per year and growth rate, endpoint MNV area or endpoint activity status for any MNV type. There was no significant association between the development of atrophy and the number of injections, baseline MNV area, baseline vessel density, or lesion growth rate. CONCLUSIONS: In nAMD, complete regression of an MNV network exposed to anti-VEGF is rare. This work emphasizes the role of anti-VEGF as anti-leakage rather than vascular regression agents in nAMD.

Dual Antagonism of PDGF and VEGF in Neovascular Age-Related Macular Degeneration: A Phase IIb, Multicenter, Randomized Controlled Trial.

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-naïve 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.

TYPE 2 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

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.

Chronic central serous chorioretinopathy imaged by optical coherence tomographic angiography.

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.

Polypoidal choroidal vasculopathy in tilted disk syndrome and high myopia with staphyloma.

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.

Verteporfin photodynamic therapy for choroidal neovascularization associated with toxoplasmic retinochoroiditis.

PURPOSE: To evaluate the efficacy and safety of verteporfin photodynamic therapy (V-PDT) for young adults and children with subfoveal choroidal neovascularization (CNV) associated with toxoplasmic retinochoroiditis. METHODS: Patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were treated with V-PDT and prospectively followed up. Before V-PDT and during follow-up, patients underwent visual acuity testing, complete ophthalmic examination including color photography, angiography with fluorescein and/or indocyanine green, and optical coherence tomography. The decision to retreat CNV was based on the criteria used in the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy investigation. RESULTS: Eight patients (5 males and 3 females) were treated at a mean age of 15.3 years (range, 5-31 years). CNV was 100% classic or predominantly classic in all study patients. Mean visual acuity increased from 20/225 (range, 20/400 to 20/50) to 20/123 (range, 20/200 to 20/25) during a mean follow-up period of 25 months (range, 5-49 months). Persistent closure of CNV was achieved in all eight patients (mean number of treatments, 1.75). Vascular anastomosis developed in the treated area in two patients, but there was no additional visual loss. No significant adverse effects of V-PDT were observed. CONCLUSION: V-PDT for subfoveal CNV associated with toxoplasmic retinochoroiditis appears to be effective and safe even in young adults and children. However, a longer follow-up is recommended to confirm our observations.

Optical coherence tomography in tamoxifen retinopathy.

Optical coherence tomography (OCT) is a non-invasive, transpupillary imaging technology that allows detailed analysis of the retinal structures. In a recent article, Gualino et al. reported that OCT revealed a foveolar cystoid space with focal disruption of the photoreceptors line that explains the irreversible loss of central vision in tamoxifen retinopathy. In addition to providing a better understanding of the pathogenesis of tamoxifen retinopathy, OCT screening is advisable in patients treated with tamoxifen over long periods in order to detect and prevent drug-induced retinal damage.