Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration : A Randomized Phase 2 Trial

Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Risk of Ovarian Cancer and Inherited Variants in Relapse-Associated Genes

Background: We previously identified a panel of genes associated with outcome of ovarian cancer. The purpose of the current study was to assess whether variants in these genes correlated with ovarian cancer risk. Methods and Findings: Women with and without invasive ovarian cancer (749 cases, 1,041 controls) were genotyped at 136 single nucleotide polymorphisms (SNPs) within 13 candidate genes. Risk was estimated for each SNP and for overall variation within each gene. At the gene-level, variation within MSL1 (male-specific lethal-1 homolog) was associated with risk of serous cancer (p = 0.03); haplotypes within PRPF31 (PRP31 pre-mRNA processing factor 31 homolog) were associated with risk of invasive disease (p = 0.03). MSL1 rs7211770 was associated with decreased risk of serous disease (OR 0.81, 95 % CI 0.66–0.98; p = 0.03). SNPs in MFSD7, BTN3A3, ZNF200, PTPRS, and CCND1A were inversely associated with risk (p,0.05), and there was increased risk at HEXIM1 rs1053578 (p = 0.04, OR 1.40, 95 % CI 1.02–1.91). Conclusions: Tumor studies can reveal novel genes worthy of follow-up for cancer susceptibility. Here, we found that inherited markers in the gene encoding MSL1, part of a complex that modifies the histone H4, may decrease risk of invasiv

Type 1 versus type 3 neovascularization in pigment epithelial detachments associated with age-related macular degeneration after anti-vascular endothelial growth factor therapy: a prospective study

PURPOSE To evaluate the response to aflibercept therapy for Type 1 and Type 3 neovascularization in pigment epithelial detachments associated with treatment-naive, neovascular age-related macular degeneration. METHODS In this multicentered, prospective study, eligible eyes underwent an intravitreal aflibercept injection protocol for 12 months. Visual acuity and morphologic features of the pigment epithelial detachments were compared at baseline and follow-up intervals between eyes with Type 1 versus Type 3 neovascularization. RESULTS Thirty-six eyes were analyzed. At 12 months, Type 1 lesions showed a 4.5 ± 23 Early Treatment of Diabetic Retinopathy Study letter improvement (P = 0.1665) versus a 14 ± 11 (P = 0.0072) letter improvement with Type 3 lesions. Both Type 1 and 3 eyes showed a significant decrease in pigment epithelial detachment size, subretinal fluid, and subretinal hyperreflective material; however, Type 3 eyes had a greater reduction in pigment epithelial detachment size and subretinal hyperreflective material, as well as a reduction in central retinal thickness. Type 1 eyes required an average of 1.636 (range, 1-4) injections to resolve fluid, which was greater than Type 3 eyes, which required an average of 1.143 (range, 1-2) injections (P = 0.0251). CONCLUSION Intravitreal aflibercept injections were efficacious for pigment epithelial detachments, but baseline and follow-up anatomical and functional outcomes differed in Type 1 versus Type 3 neovascularization. The better response of Type 3 eyes with fewer injections suggests that differentiation of the neovascularization subtype at the initial diagnosis may allow for a more tailored, optimal therapy

Treatment outcomes of conventional or high-dose ranibizumab for vascularized pigment epithelial detachment based on lesion subtypes

Introduction: A post hoc study was conducted to compare visual and anatomic outcomes of vascularized serous pigment epithelial detachment (Group 1) with fibrovascular pigment epithelial detachment (Group 2) due to age-related macular degeneration treated with either 0.5 or 2.0 mg ranibizumab injections. Methods: A prospective, randomized trial was performed with the following regimens for 12 months: (1) 0.5 mg monthly, (2) 0.5 mg monthly for 4 months followed by pro re nata injections, (3) 2.0 mg monthly, and (4) 2.0 mg monthly for 4 months followed by pro re nata injections. Primary measure was best-corrected standardized vision. Secondary measures included central subfield, thickness surface area A2, greatest linear diameter, heights of pigment epithelial detachment and choroidal neovascularization (CNV), subretinal fluid, cystoid macular edema, and adverse events. Results: For 36 eyes (8 in Group 1 and 28 in Group 2), follow-up time was 12 months. There were no differences in baseline features between groups except for pigment epithelial detachment A2 (Group 2 &gt; Group 1). Two-way analysis of variance showed comparable improvements in anatomic and vision outcomes. Three-way analysis of variance also showed similar responses for both lesion subtypes with high-dose treatment. There was a trend toward greater pigment epithelial detachment resolution in Group 1 eyes. There were no differences in retinochoroidal angiomatous proliferation (Type-3 CNV) and cataracts between groups, although greater percentages of eyes in Group 1 developed retinal pigment epithelial tears (25% vs 10.7%). Conclusion: There were no differences in vision and anatomic outcomes between lesion subtypes, and similarly, more rapid responses to high-dose than conventional-dose ranibizumab occurred for eyes with both lesion subtypes. More retinal pigment epithelial tears may develop in eyes with vascularized serous pigment epithelial detachment. </jats:sec